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CARBOplatin

Medically reviewed by Drugs.com. Last updated on Sep 22, 2019.

Pronunciation

(KAR boe pla tin)

Index Terms

  • CBDCA
  • Paraplatin

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 150 mg/15 mL (15 mL [DSC]); 450 mg/45 mL (45 mL [DSC]); 600 mg/60 mL (60 mL [DSC])

Solution, Intravenous [preservative free]:

Generic: 50 mg/5 mL (5 mL); 150 mg/15 mL (15 mL); 450 mg/45 mL (45 mL); 600 mg/60 mL (60 mL)

Pharmacologic Category

  • Antineoplastic Agent, Alkylating Agent
  • Antineoplastic Agent, Platinum Analog

Pharmacology

Carboplatin is a platinum compound alkylating agent which covalently binds to DNA; interferes with the function of DNA by producing interstrand DNA cross-links. Carboplatin is apparently not cell-cycle specific.

Distribution

Vd: 16 L (based on a dose of 300 to 500 mg/m2); into liver, kidney, skin, and tumor tissue

Metabolism

Minimally hepatic to aquated and hydroxylated compounds

Excretion

Urine (~70% as carboplatin within 24 hours; 3% to 5% as platinum within 1 to 4 days)

Half-Life Elimination

CrCl >60 mL/minute: Carboplatin: 2.6 to 5.9 hours (based on a dose of 300 to 500 mg/m2); Platinum (from carboplatin): ≥5 days

Protein Binding

Carboplatin: 0%; Platinum (from carboplatin): Irreversibly binds to plasma proteins

Special Populations: Renal Function Impairment

In patients with CrCl <60 mL/minute, the total body and renal clearance decreases as CrCl decreases.

Use: Labeled Indications

Ovarian cancer, advanced: Initial treatment of advanced ovarian cancer in combination with other established chemotherapy agents; palliative treatment of recurrent ovarian cancer after prior chemotherapy, including cisplatin-based treatment

Off Label Uses

Anal cancer (advanced)

Data from two small studies (one phase II and one retrospective) support the use of carboplatin (in combination with paclitaxel or paclitaxel and fluorouracil) for the treatment of advanced anal cancer [Hainsworth 2001], [Kim 2014].

Bladder cancer

Data from two phase II studies support the use of carboplatin (in combination with gemcitabine or paclitaxel) in the treatment of advanced transitional cell urothelium cancer [Bamias 2006], [Vaughn 2002].

Breast cancer (metastatic)

Data from two multicenter, randomized phase III studies support the use of carboplatin (in combination with docetaxel and trastuzumab or with paclitaxel and trastuzumab) in the treatment of HER-2 overexpressing metastatic breast cancer [Robert 2006], [Valero 2011]. Data from two earlier phase II studies also support the use of carboplatin in combination with docetaxel and trastuzumab [Peagram 2004].

Cervical cancer (recurrent or metastatic)

Data from three studies support the use of carboplatin (in combination with paclitaxel or as a single agent) in the treatment of advanced/metastatic or recurrent cervical cancer [Pectasides 2009], [Tinker 2005], [Weiss 1990].

Endometrial cancer (advanced or recurrent)

Data from several studies support the use of carboplatin (in combination with paclitaxel) in the treatment of advanced/metastatic or recurrent endometrial cancer [Miller 2012], [Pectasides 2008], [Secord 2007]. Data from a small randomized, controlled phase II study support the use of carboplatin (in combination with paclitaxel and trastuzumab) for the treatment of advanced (stage III or IV) or recurrent, HER2-positive endometrial (uterine serous) cancer [Fader 2018].

Esophageal cancer

Data from a phase III trial support the use of carboplatin (in combination with paclitaxel and radiation) as preoperative chemoradiotherapy for the treatment of esophageal or esophagogastric junction cancer [van Hagen 2012]. Data from two phase II studies also support the use of carboplatin (in combination with paclitaxel) in the treatment of esophageal cancer [El-Rayes 2004], [van Meerten 2006].

Gastric cancer

Data from a phase III trial support the use of carboplatin (in combination with paclitaxel and radiation) as preoperative chemoradiotherapy for the treatment of esophageal or esophagogastric junction cancer [van Hagen 2012]. A small phase II study also suggests that carboplatin (in combination with paclitaxel) is an active and well-tolerated regimen in patients with advanced gastric cancer [Gadgeel 2003].

Head and neck cancer

Data from a phase III randomized study support the use of carboplatin (in combination with fluorouracil) for the treatment of advanced squamous cell head and neck cancer [Forastiere 1992]. Data from a phase III randomized study supports the use of carboplatin (in combination with fluorouracil and cetuximab) as first-line treatment of recurrent or metastatic squamous cell head and neck cancer [Vermorken 2008]. Data from a phase II study supports the use of carboplatin (in combination with paclitaxel) in the treatment of advanced head and neck cancer [Clark 2001]. Data from a phase II study supports the use of carboplatin (in combination with cetuximab) in the treatment of recurrent or metastatic nasopharyngeal cancer [Chan 2005]. Data from randomized phase III trials support the use of weekly carboplatin (in combination with radiation) following induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) for the treatment of advanced head and neck cancer [Haddad 2013], [Posner 2007].

Hematopoietic stem cell transplant

Data from a retrospective study suggest that carboplatin (in combination with etoposide) followed by autologous stem cell transplant may be beneficial for the treatment of metastatic testicular cancer [Einhorn 2007].

Hodgkin lymphoma (relapsed or refractory)

Data from a study of multimodality therapy in chemosensitive Hodgkin lymphoma support the use of carboplatin (in combination with ifosfamide and etoposide, followed by autologous stem cell transplant) as salvage treatment of relapsed and refractory Hodgkin lymphoma [Moskowitz 2001].

Malignant pleural mesothelioma

Data from two phase II studies support the use of carboplatin (in combination with pemetrexed) in the treatment of malignant pleural mesothelioma [Castagneto 2008], [Ceresoli 2006].

Melanoma (advanced or metastatic)

Data from a retrospective review suggest that carboplatin (in combination with paclitaxel) may be beneficial as a second-line regimen for the treatment of advanced or metastatic melanoma [Rao 2006].

Merkel cell carcinoma

Data from a phase II study in patients with high-risk Merkel cell carcinoma of the skin suggest that synchronous radiation in combination with carboplatin and etoposide chemotherapy results in high levels of locoregional and distant control, as well as survival [Poulsen 2003]. Data from another small study supports the use of weekly carboplatin administered concurrently with radiation, followed by combination chemotherapy with carboplatin and etoposide after radiation completion for the treatment of Merkel cell carcinoma with high-risk features [Poulsen 2008].

Neuroendocrine tumors, advanced, atypical or poorly differentiated (nonpulmonary)

Clinical data and consensus guideline recommendations from the North American Neuroendocrine Tumor Society (NANETS) suggest that regimens active in the treatment of small cell lung cancer (eg, carboplatin and etoposide) may be effective for the management of atypical or poorly differentiated (nonpulmonary) neuroendocrine tumors [Skarlos 2001], [Sorbye 2013], [Strosberg 2010].

Non-Hodgkin lymphomas (relapsed or refractory)

Data from a small study support the use of carboplatin (in combination with rituximab, ifosfamide and etoposide) as second-line therapy to induce a response in the treatment of relapsed or refractory diffuse large b-cell lymphoma (DLBCL) prior to autologous stem cell transplant [Kewalramani 2004].

Non-small cell lung cancer

Data from a large randomized phase III study support the use of carboplatin (in combination with paclitaxel and bevacizumab) in recurrent or advanced non-squamous non-small cell lung cancer (NSCLC) [Sandler 2006]. Data from a large randomized study support the use of carboplatin (in combination with paclitaxel) in advanced NSCLC [Schiller 2002]. Data from a subset analysis support the use of carboplatin (in combination with paclitaxel) in elderly patients with advanced NSCLC [Ramalingam 2008]. Data from a large randomized study support the use of carboplatin (in combination with paclitaxel) in the adjuvant treatment of NSCLC in patients with tumors ≥4 cm [Strauss 2008]. Data from a large randomized phase III study support the use of carboplatin (in combination with or pemetrexed) as first-line therapy in advanced NSCLC [Gronberg 2009]. Data from a large double-blind randomized phase III study and from a multicenter randomized phase II study support the use of carboplatin (in combination with pemetrexed and pembrolizumab) in the management of previously untreated advanced (stage IIIB or IV) non-squamous NSCLC without EGFR mutations or ALK translocations [Gandhi 2018], [Langer 2016]. Data from a randomized phase II study support the use of carboplatin (in combination with radiation therapy and paclitaxel) in the treatment of locally advanced NSCLC [Belani 2005]. Another large phase III study supports the use of carboplatin (in combination with bevacizumab and pemetrexed) for the treatment of advanced non-squamous NSCLC [Patel 2013]. Data from another randomized phase III study support the use of carboplatin (in combination with atezolizumab, bevacizumab, and paclitaxel) as first-line treatment of metastatic NSCLC or recurrent metastatic non-squamous NSCLC (previously untreated with chemotherapy) in patients without EGFR or ALK genomic tumor alterations or with EGFR or ALK alterations and disease progression on or intolerance to a tyrosine kinase inhibitor [Socinski 2018]. Data from a large double-blind randomized phase III trial support the use of carboplatin (in combination with pembrolizumab and either paclitaxel or paclitaxel [protein bound]) as first-line treatment of metastatic squamous cell NSCLC [Paz-Ares 2018].

Based on American Society of Clinical Oncology Guidelines, for Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer, platinum (doublet) therapy is recommended as first-line therapy for stage IV NSCLC in patients with a performance status of 1 or 0.

Sarcomas (Ewing sarcoma and osteosarcoma)

Data from a study in patients ≤22 years of age with recurrent/refractory sarcomas (including Ewing and osteosarcoma), support the use of carboplatin (in combination with ifosfamide and etoposide) as reinduction therapy in the treatment of this condition [van Winkle 2005].

Small cell lung cancer

Data from a randomized phase III study support the use of carboplatin (in combination with irinotecan) for the treatment of extensive stage small cell lung cancer (SCLC) [Hermes 2008]. Data from a randomized, double-blind, placebo-controlled phase III study support the use of carboplatin (in combination with etoposide and atezolizumab) for the treatment of extensive-stage SCLC in previously untreated patients [Horn 2018]. Data from a phase 2 study also support the use of carboplatin (in combination with irinotecan) for the treatment of extensive stage SCLC [Schmittel 2006].

Data from a randomized phase II study support the use of carboplatin (in combination with etoposide and radiation therapy) for the treatment of limited stage SCLC [Skarlos 2001].

Based on American Society of Clinical Oncology Guidelines, for Treatment of Small-Cell Lung Cancer, platinum-based therapy in combination with either etoposide or irinotecan is recommended over other chemotherapy regimens for limited stage or extensive stage disease [Rudin 2015].

Testicular cancer

Data from a large randomized trial support the use of carboplatin (as a one-time dose) as adjuvant treatment of stage I seminoma [Oliver 2011].

Data from a retrospective study suggest that carboplatin (in combination with etoposide) followed by autologous stem cell transplant may be beneficial for the treatment of metastatic testicular cancer [Einhorn 2007].

Thymic malignancies

Data from a phase II study support the use of carboplatin (in combination with paclitaxel) in the treatment of advanced thymoma or thymic carcinoma [Lemma 2008].

Thyroid cancer (anaplastic), advanced

Data from a randomized phase III trial support the use of carboplatin (in combination with paclitaxel) for the treatment of advanced anaplastic thyroid cancer [Sosa 2014].

The American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer suggest that carboplatin (in combination with paclitaxel) may be used in the treatment of this condition [Smallridge 2012].

Unknown primary adenocarcinoma

Data from a multicenter phase II study support the use of carboplatin (in combination with paclitaxel) in the treatment of unknown primary adenocarcinoma [Briasoulis 2000]. Data from a smaller phase II study also support the use of carboplatin (in combination with docetaxel) in the management of unknown primary adenocarcinoma [Greco 2000]. Data from a prospective, multicenter, phase II study in patients with metastatic poorly differentiated neuroendocrine carcinoma (62% with unknown primary site) who had received no prior treatment demonstrated that carboplatin (in combination with paclitaxel and etoposide) is effective for the management of this condition [Hainsworth 2006].

Contraindications

History of severe allergic reaction to carboplatin, cisplatin, other platinum-containing formulations, or any component of the formulation; should not be used in patients with severe bone marrow depression or significant bleeding.

Canadian labeling: Additional contraindications (not in the US labeling): Preexisting severe renal impairment.

Dosing: Adult

Note: Doses for adults are commonly calculated by the target AUC using the Calvert formula, where Total dose (mg) = Target AUC x (GFR + 25). If estimating GFR instead of a measured GFR, the FDA recommends that clinicians consider capping estimated GFR at a maximum of 125 mL/minute to avoid potential toxicity. Antiemetics may be recommended to prevent nausea and vomiting; carboplatin is associated with a moderate to high emetic potential (dose/AUC dependent) (Hesketh 2017; Roila 2016).

Anal cancer, advanced (off-label use; based on limited data): IV: Target AUC 6 on days 1 and 22 every 6 weeks for up to 4 cycles (in combination with paclitaxel and fluorouracil) (Hainsworth 2001) or Target AUC 5 or 6 every 3 weeks (in combination with paclitaxel) (Kim 2014).

Bladder cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with gemcitabine) (Bamias 2006) or Target AUC 6 every 3 weeks (in combination with paclitaxel) (Vaughn 2002).

Breast cancer, metastatic (off-label use): IV: Target AUC 6 every 3 weeks (in combination with trastuzumab and paclitaxel) (Robert 2006) or Target AUC 6 every 3 weeks (in combination with trastuzumab and docetaxel) (Pegram 2004; Valero 2011).

Cervical cancer, recurrent or metastatic (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Pectasides 2009) or Target AUC 5 to 6 every 4 weeks (in combination with paclitaxel) (Tinker 2005) or 400 mg/m2 every 28 days (as a single agent) (Weiss 1990).

Endometrial cancer, advanced or recurrent (off-label use): IV: Target AUC 6 every 3 weeks (in combination with paclitaxel) for 7 cycles (Miller 2012) or Target AUC 5 every 3 weeks (in combination with paclitaxel) for 6 to 9 cycles or until disease progression or unacceptable toxicity (Pectasides 2008) or Target AUC 2 on days 1, 8, and 15 every 28 days (in combination with paclitaxel) until disease progression or unacceptable toxicity (Secord 2007) or (for HER2+ uterine serous cancer) Target AUC 5 every 3 weeks (in combination with paclitaxel and trastuzumab) for ~6 cycles, followed by trastuzumab maintenance therapy (Fader 2018).

Esophageal cancer (off-label use): IV: Target AUC 2 once weekly for 5 weeks (in combination with paclitaxel and radiation therapy) prior to surgery (van Hagen 2012; van Meerten 2006) or Target AUC 5 every 3 weeks (in combination with paclitaxel) (El-Rayes 2004).

Gastric cancer (off-label use): IV: Target AUC 2 once weekly for 5 weeks (in combination with paclitaxel and concurrent radiation) prior to surgery (van Hagen 2012) or Target AUC 5 to 6 every 3 weeks (in combination with paclitaxel) (Gadgeel 2003).

Head and neck cancer (off-label use): IV: Target AUC 5 every 3 weeks (in combination with cetuximab) (Chan 2005) or Target AUC 5 every 3 weeks (in combination with cetuximab and fluorouracil) (Vermorken 2008) or 300 mg/m2 every 4 weeks (in combination with fluorouracil) (Forastiere 1992) or Target AUC 6 every 3 weeks (in combination with paclitaxel) (Clark 2001) or Target AUC 1.5 weekly for 7 weeks (in combination with radiation, following 3 cycles of docetaxel, cisplatin, and fluorouracil [TPF] induction therapy [begin carboplatin/radiation therapy 3 to 8 weeks after the start of TPF cycle 3]) (Haddad 2013; Posner 2007).

Hematopoietic stem cell transplant for metastatic germ cell tumors (off-label use; based on limited data): IV: 700 mg/m2/day for 3 days beginning 5 days prior to peripheral stem cell infusion (in combination with etoposide) for 2 cycles (Einhorn 2007).

Hodgkin lymphoma, relapsed or refractory (off-label use): IV: Target AUC 5 (maximum dose: 800 mg) for 2 cycles (in combination with ifosfamide and etoposide) (Moskowitz 2001).

Malignant pleural mesothelioma (off-label use): IV: Target AUC 5 every 3 weeks (in combination with pemetrexed) (Castagneto 2008; Ceresoli 2006).

Melanoma, advanced or metastatic (off-label use; based on limited data): IV: Target AUC 2 days on 1, 8, and 15 every 4 weeks (in combination with paclitaxel) (Rao 2006).

Merkel cell carcinoma (off-label use): IV: Target AUC 4.5 on day 1 of weeks 1, 4, 7, and 10 (in combination with etoposide and synchronous radiation therapy) (Poulsen 2003) or Target AUC 2 on day 1 weekly for up to 5 doses (administered concurrently with radiation), followed (beginning 3 weeks after radiation therapy) by carboplatin with a target AUC of 4.5 on day 1 (in combination with etoposide) every 3 weeks for 3 cycles (Poulsen 2008).

Neuroendocrine tumors, advanced, atypical or poorly differentiated (nonpulmonary) (off-label use): IV: Target AUC 6 every 3 weeks (in combination with etoposide) for 4 to 6 cycles (Skarlos 2001; Strosberg 2010).

Non-Hodgkin lymphomas, relapsed or refractory (off-label use): IV: Target AUC 5 (maximum dose: 800 mg) per cycle for 3 cycles (in combination with rituximab, ifosfamide and etoposide) (Kewalramani 2004).

Non-small cell lung cancer (off-label use): IV: Target AUC 6 every 3 to 4 weeks (in combination with paclitaxel) (Ramalingam 2008; Schiller 2002; Strauss 2008) or Target AUC 6 every 3 weeks (in combination with bevacizumab and paclitaxel) (Sandler 2006) or Target AUC 5 every 3 weeks (in combination with pemetrexed) (Gronberg 2009) or Target AUC 6 every 3 weeks (in combination with pemetrexed and bevacizumab) for up to 4 cycles followed by maintenance therapy (Patel 2013) or Target AUC 5 every 3 weeks (in combination with pemetrexed and pembrolizumab) for 4 cycles followed by pembrolizumab/pemetrexed maintenance therapy (Gandhi 2018; Langer 2016) or Target AUC 6 every 3 weeks for 4 cycles (in combination with pembrolizumab and either paclitaxel or paclitaxel [protein bound]) followed by pembrolizumab maintenance therapy (Paz-Ares 2018) or Target AUC 6 every 3 weeks for 4 to 6 cycles (in combination with atezolizumab, bevacizumab, and paclitaxel) followed by atezolizumab/bevacizumab maintenance therapy (Socinski 2018) or in combination with radiation therapy and paclitaxel (Belani 2005):

Target AUC 6 every 3 weeks for 2 cycles or

Target AUC 6 every 3 weeks for 2 cycles; then target AUC 2 weekly for 7 weeks or

Target AUC 2 every week for 7 weeks; then target AUC 6 every 3 weeks for 2 cycles.

Ovarian cancer, advanced:

Advanced ovarian cancer (off-label dosing):IV: Target AUC 5 to 7.5 every 3 weeks (in combination with paclitaxel) (Ozols 2003; Parmar 2003) or Target AUC 2 once weekly (in combination with weekly paclitaxel) for 18 consecutive weeks (Pignata 2014) or Target AUC 5 every 3 weeks (in combination with docetaxel) (Vasey 2004) or Target AUC 6 on day 1 every 3 weeks (in combination with bevacizumab [delayed until cycle 2] and paclitaxel) for up to 6 cycles, followed by bevacizumab monotherapy for a total of up to 22 cycles or until disease progression (whichever occurs earlier) (Burger 2011).

Neoadjuvant therapy (off-label schedule): Note: According to guidelines from the Society of Gynecologic Oncology (SGO) and American Society of Clinical Oncology (ASCO) for neoadjuvant chemotherapy in newly diagnosed advanced ovarian cancer, neoadjuvant therapy should be utilized only in properly selected patients. Selection criteria include patients with newly diagnosed suspected stage IIIC or IV ovarian cancer who have a high perioperative risk profile and/or a low likelihood of achieving cytoreduction to <1 cm of residual disease (SGO/ASCO [Wright 2016]).

IV: AUC 5 or 6 on day 1 every 3 weeks (either as a single agent or in combination with paclitaxel) for 3 neoadjuvant cycles, followed by debulking surgery, followed by 3 additional chemotherapy cycles (Kehoe 2015) or AUC 5 on day 1 every 3 weeks (in combination with paclitaxel) for 3 neoadjuvant cycles, followed by debulking surgery, followed by 3 additional chemotherapy cycles (Vergote 2010) or AUC 5 on day 1 every 3 weeks (in combination with paclitaxel) for 3 to 4 neoadjuvant cycles, followed by debulking surgery, followed by 2 to 3 additional chemotherapy cycles, for a total of 6 cycles (Fagotti 2016).

Malignant germ cell tumor (off-label dosing): IV: 400 mg/m2 on day 1 (in combination with etoposide) every 4 weeks for 3 cycles (Williams 2004).

Manufacturer's labeling: IV: Dosing in the prescribing information may not reflect current clinical practice. 360 mg/m2 every 4 weeks (as a single agent) or 300 mg/m2 every 4 weeks (in combination with cyclophosphamide) for 6 cycles or Target AUC 4 to 6 (single agent; in previously treated patients).

Sarcomas: Ewing sarcoma, osteosarcoma (off-label uses): Adults ≤22 years of age: IV: 400 mg/m2/day for 2 days every 21 days (in combination with ifosfamide and etoposide) (van Winkle 2005).

Small cell lung cancer (off-label use): IV:

Extensive stage disease: Target AUC 5 every 3 weeks (in combination with irinotecan) (Hermes 2008) or Target AUC 5 every 28 days (in combination with irinotecan) (Schmittel 2006) or Target AUC 5 on day 1 every 3 weeks (in combination with etoposide and atezolizumab) for 4 induction cycles, followed by atezolizumab maintenance therapy (Horn 2018).

Limited stage disease: Target AUC 6 every 3 weeks (in combination with etoposide) (Skarlos 2001).

Testicular cancer (off-label use): IV: Target AUC 7 as a one-time dose (Oliver 2011) or 700 mg/m2/day for 3 days beginning 5 days prior to peripheral stem cell infusion (in combination with etoposide) for 2 cycles (Einhorn 2007).

Thymic malignancies (off-label use): IV: Target AUC 5 every 3 weeks (in combination with paclitaxel) (Lemma 2008).

Thyroid cancer (anaplastic), advanced (off-label use): IV: Target AUC 6 on day 1 every 3 weeks (in combination with paclitaxel) for 6 cycles (Smallridge 2012; Sosa 2014) or Target AUC 2 once weekly (in combination with weekly paclitaxel) (Smallridge 2012).

Unknown primary adenocarcinoma (off-label use): IV: Target AUC 6 every 3 weeks (in combination with paclitaxel) (Briasoulis 2000) or Target AUC 6 every 3 weeks (in combination with docetaxel) (Greco 2000) or Target AUC 6 every 3 weeks (in combination with paclitaxel and etoposide) (Hainsworth 2006).

Dosing: Geriatric

The Calvert formula should be used to calculate dosing for elderly patients. Refer to adult dosing.

Dosing: Pediatric

Note: Dosing and frequency may vary by protocol and/or treatment phase; refer to specific protocol. In pediatric patients, dosing may be based on either BSA (mg/m2), weight (mg/kg), or a modified Calvert formula calculation (mg); use extra precaution to verify dosing parameters and units of GFR/estimated CrCl during calculations, as errors can lead to significant over/under dosing. Some protocols suggest weight or age cut-offs for weight-based (mg/kg) dosing; refer to specific protocol. Carboplatin is associated with a high emetic potential in pediatric patients (Dupuis 2011); antiemetics are recommended to prevent nausea and vomiting (Dupuis 2013).

Calvert Formula, modified: Limited data available; multiple formulas have been used; formula may be protocol-specific (Liem 2003): Some protocols may calculate pediatric carboplatin doses using one of the following modified Calvert formulas:

Modified Calvert Formulas

Target AUC: Protocol specific dependent upon indication; value presented in terms of mg/mL and minute units (eg, mg/mL/minute or mg/mL•minute are frequently reported).

Note: Ensure appropriate GFR valueA is used for calculation and resulting carboplatin dose (mg or mg/m2) units.

Newell formula

(Newell 1993)

Total dose (mg) = Target AUC x [uncorrected or raw GFR (mL/minute) + (0.36 x kg body weight)]

Mann/Pein formula

(Mann 1998; Mann 2000; Pein 1998)

Total dose (mg) = Target AUC x [uncorrected or raw GFR (mL/minute) + (15 x BSA(m2))]

Marina/St. Jude formulaB

(Allen 2010; Marina 1993)

Dose (mg/m2) = Target AUC x [(0.93 x corrected GFR normalized to patient’s BSA (mL/minute/m2 )) + 15]

AGFR definitions:

Raw GFR = uncorrected GFR = mL/minute

Normalized GFR = corrected GFR = mL/minute/1.73 m2

BMarina/St. Jude formula: Uses a corrected GFR normalized to patient’s BSA (mL/minute/m2); converting GFR to this may be done as follows:

Corrected GFR (mL/minute/1.73 m2)/1.73 = GFR (mL/minute/m2)

Uncorrected GFR (mL/minute)/patient’s BSA = GFR (mL/minute/m2)

Note: Calvert formula was based on using chromic edetate (51Cr-EDTA) plasma clearance to establish GFR. This or 99mTc- DTPA nuclear medicine GFR study is preferred over estimating CrCl per Schwartz equation as CrCl theoretically exceeds measured GFR by >12% in subjects with normal renal function (Allen 2010) (see Warnings/Precautions for additional information).

Hematopoietic stem cell transplant (HSCT): Limited data available:

Cohen 2015: Consolidation with myeloablative chemotherapy: Infants ≥6 months and Children ≤3 years: IV: 17 mg/kg over 2 hours on days 0 and 1 of a 21-day cycle in combination with thiotepa for 3 cycles.

Gilheeney 2010, Kushner 2001: Myeloablative: Children and Adolescents: IV: ~500 mg/m2 over 4 hours for 3 doses on days -5 to -3; dosing utilized Calvert formula with a target AUC=7 in combination regimen with thiotepa and topotecan

Spreafico 2008: Consolidation after reinduction chemo (relapsed Wilms Tumor): Children <12 years: IV: 200 mg/m2 for 4 doses on days -6 to -3 in combination with melphalan and etoposide

Glioma: Limited data available (Packer 1997): Infants ≥3 months, Children, and Adolescents:

Induction: IV: 175 mg/m2 once weekly for 4 weeks every 6 weeks (2-week recovery period between courses) in combination with vincristine for 2 cycles

Maintenance: IV: 175 mg/m2 weekly for 4 weeks, with a 3-week recovery period between courses in combination with vincristine for ≤12 cycles

Neuroblastoma, localized and unresectable: Limited data available:

Infants: IV: 6.6 mg/kg on days 1, 2, and 3 in combinations with etoposide for 2 cycles (CE regimen), followed by cyclophosphamide, doxorubicin, and vincristine (CAdO regimen) (Rubie 2001)

Children <10 kg: IV: 100 to 140 mg/m2/day on days 1, 2, and 3 every 21 days in combination with etoposide for 2 cycles (CE regimen), followed by cyclophosphamide, doxorubicin, and vincristine (CAdO regimen) (Rubie 1998)

Children ≥10 kg and Adolescents: IV: 200 mg/m2/day on days 1, 2, and 3 every 21 days in combination with etoposide for 2 cycles (CE regimen), followed by cyclophosphamide, doxorubicin, and vincristine (CAdO regimen) (Rubie 1998)

Retinoblastoma: Limited data available:

Rodriguez-Galindo 2003: Infants and Children:

GFR ≥50 mL/minute/m2: IV: 560 mg/m2 in combination with vincristine every 21 days for 8 cycles

GFR <50 mL/minute/m2: IV: Dosing utilized modified Calvert formula with a target AUC=6.5 in combination regimen with vincristine every 21 days for 8 cycles

Friedman 2000:

Infants and Children ≤3 years: IV: 18.6 mg/kg on day 0 every 28 days in combination with etoposide and vincristine for 6 cycles (VEC regimen)

Children >3 years: IV: 560 mg/m2 on day 0 every 28 days in combination with etoposide and vincristine for 6 cycles (VEC regimen)

Sarcomas; Ewing sarcoma, osteosarcoma: Children and Adolescents: IV: 400 mg/m2/day for 2 days every 21 days in combination with ifosfamide and etoposide (ICE regimen) (Van Winkle 2005)

Wilms tumor, relapsed or refractory:

Abu-Ghosh 2002; Daw 2009: Children and Adolescents: IV: 400 mg/m2/day for 2 days or modified Calvert using Marina/St. Jude formula with a target AUC=6 for 1 day in combination with ifosfamide and etoposide every 21 days (ICE regimen)

Spreafico 2008: Reinduction prior to autologous stem cell rescue: Children <12 years: IV: 600 mg/m2 for 1 dose in combination with ifosfamide and etoposide

Dosing adjustment for toxicity: The presented dosing adjustments are based on experience in adult patients; specific recommendations for pediatric patients are limited. Refer to specific protocol for management in pediatric patients if available.

Adult: Post-treatment nadir: Platelets <50,000 cells/mm3 or ANC <500 cells/mm3: Administer 75% of dose

Dosing: Adjustment for Toxicity

Platelets <50,000 cells/mm3 or ANC <500 cells/mm3: Administer 75% of the usual dose

Dosing: Obesity

American Society of Clinical Oncology (ASCO) Guidelines for appropriate chemotherapy dosing in obese adults with cancer (excludes HSCT dosing): Dosing based on GFR should be considered in obese patients; GFR should not exceed 125 mL/minute (Griggs 2012).

American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) for calculation of body surface area (when applicable) in carboplatin dosing for hematopoietic stem cell transplant conditioning regimens in adults. Based on the literature, there is no consensus for carboplatin dosing based on AUC in transplant conditioning regimens or dosing adjustments during transplant for obese patients (Bubalo 2014).

Reconstitution

Solution for injection: Manufacturer's labeling states solution can be further diluted to concentrations as low as 0.5 mg/mL in NS or D5W; however, most clinicians generally dilute dose in either 100 mL or 250 mL of NS or D5W.

Concentrations used for desensitization vary based on protocol.

Needles or IV administration sets that contain aluminum should not be used in the preparation or administration of carboplatin; aluminum can react with carboplatin resulting in precipitate formation and loss of potency.

Administration

Antiemetics may be recommended to prevent nausea and vomiting; depending on the dose, carboplatin is associated with a moderate to high emetic potential in adults (Hesketh 2017; Roila 2016).

IV: Infuse over at least 15 minutes; usually infused over 15 to 60 minutes, although some protocols may require infusions up to 24 hours. When administered as a part of a combination chemotherapy regimen, sequence of administration may vary by regimen; refer to specific protocol for sequence recommendation.

Needles or IV administration sets that contain aluminum should not be used in the preparation or administration of carboplatin; aluminum can react with carboplatin resulting in precipitate formation and loss of potency.

Storage

Store intact vials at room temperature at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Further dilution to a concentration as low as 0.5 mg/mL is stable at room temperature (25°C) for 8 hours in NS or D5W. Stability has also been demonstrated for dilutions in D5W in PVC bags at room temperature for 9 days (Benaji 1994); however, the manufacturer recommends use within 8 hours due to lack of preservative. Multidose vials are stable for up to 14 or 15 days after opening when stored at 25°C (77°F) following multiple needle entries (refer to specific product labeling for stability information).

Drug Interactions

Aminoglycosides: May enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bexarotene (Systemic): CARBOplatin may increase the serum concentration of Bexarotene (Systemic). Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosphenytoin-Phenytoin: Platinum Derivatives may decrease the serum concentration of Fosphenytoin-Phenytoin. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

SORAfenib: May enhance the adverse/toxic effect of CARBOplatin. Management: Concurrent sorafenib with carboplatin and paclitaxel in patients with squamous cell lung cancer is contraindicated. Use in other settings is not specifically contraindicated but should be approached with added caution. Avoid combination

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Taxane Derivatives: Platinum Derivatives may enhance the myelosuppressive effect of Taxane Derivatives. Administer Taxane derivative before Platinum derivative when given as sequential infusions to limit toxicity. Consider therapy modification

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Topotecan: Platinum Derivatives may enhance the adverse/toxic effect of Topotecan. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

Percentages reported with single-agent therapy.

>10%:

Central nervous system: Pain (23%)

Endocrine & metabolic: Hyponatremia (29% to 47%), hypomagnesemia (29% to 43%), hypocalcemia (22% to 31%), hypokalemia (20% to 28%)

Gastrointestinal: Vomiting (65% to 81%), abdominal pain (17%), nausea (without vomiting: 10% to 15%)

Hematologic & oncologic: Bone marrow depression (dose related and dose limiting; nadir at ~21 days with single-agent therapy), anemia (71% to 90%; grades 3/4: 21%), leukopenia (85%; grades 3/4: 15% to 26%), neutropenia (67%; grades 3/4: 16% to 21%), thrombocytopenia (62%; grades 3/4: 25% to 35%)

Hepatic: Increased serum alkaline phosphatase (24% to 37%), increased serum AST (15% to 19%)

Hypersensitivity: Hypersensitivity (2% to 16%)

Neuromuscular & skeletal: Weakness (11%)

Renal: Decreased creatinine clearance (27%), increased blood urea nitrogen (14% to 22%)

1% to 10%:

Central nervous system: Peripheral neuropathy (4% to 6%), neurotoxicity (5%)

Dermatologic: Alopecia (2% to 3%)

Gastrointestinal: Constipation (6%), diarrhea (6%), dysgeusia (1%), mucositis (≤1%), stomatitis (≤1%)

Hematologic & oncologic: Bleeding complications (5%), hemorrhage (5%)

Hepatic: Increased serum bilirubin (5%)

Infection: Infection (5%)

Ophthalmic: Visual disturbance (1%)

Otic: Ototoxicity (1%)

Renal: Increased serum creatinine (6% to 10%)

<1%, postmarketing, and/or case reports (Limited to important or life-threatening): Anaphylaxis, anorexia, bronchospasm, cardiac failure, cerebrovascular accident, dehydration, embolism, erythema, febrile neutropenia, hemolytic anemia (acute), hemolytic-uremic syndrome, hypertension, hypotension, injection site reaction (pain, redness, swelling), limb ischemia (acute), malaise, metastases, pruritus, skin rash, tissue necrosis (associated with extravasation), urticaria, vision loss

ALERT: U.S. Boxed Warning

Experienced physician:

Carboplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.

Bone marrow suppression:

Bone marrow suppression is dose related and may be severe, resulting in infection or bleeding. Anemia may be cumulative and may require transfusion support.

Vomiting:

Vomiting is a frequent drug-related side effect.

Hypersensitivity reactions:

Anaphylactic-like reactions to carboplatin have been reported and may occur within minutes of carboplatin administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression, which may be severe, is dose related; may result in infection (due to neutropenia) or bleeding (due to thrombocytopenia); anemia may require blood transfusion. Reduce dosage in patients with bone marrow suppression; cycles should be delayed until WBC and platelet counts have recovered. In patients receiving single agent carboplatin, the median nadir typically occurs at day 21. Patients who have received prior myelosuppressive therapy and patients with renal dysfunction are at increased risk for bone marrow suppression. Anemia is cumulative. Monitor blood counts closely.

• GI toxicity: [US Boxed Warning]: Vomiting may occur. Antiemetics may be recommended to prevent nausea and vomiting; depending on the dose, carboplatin is associated with a moderate to high emetic potential in adults and a high emetic potential in pediatric patients (Hesketh 2017; Paw Cho Sing 2019; Roila 2016). Nausea and vomiting may be more severe in patients who have received prior emetogenic therapy.

• Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Anaphylactic-like reactions have been reported with carboplatin; may occur within minutes of administration. Epinephrine, corticosteroids, and antihistamines have been used to treat symptoms. The risk of allergic reactions (including anaphylaxis) is increased in patients previously exposed to platinum therapy. Skin testing and desensitization protocols have been reported (Confina-Cohen 2005; Lee 2004; Markman 2003).

• Liver function abnormalities: High doses (>4 times the recommended dose) have resulted in severe abnormalities of liver function tests.

• Neurotoxicity: Although peripheral neuropathy occurs infrequently, the incidence of peripheral neuropathy is increased in patients >65 years of age and those who have previously received cisplatin treatment.

• Ototoxicity: Ototoxicity may occur when administered concomitantly with aminoglycosides. Clinically significant hearing loss has been reported to occur in pediatric patients when therapy was administered at higher-than-recommended doses in combination with other ototoxic agents (eg, aminoglycosides). In a study of children receiving carboplatin for the treatment of retinoblastoma, those <6 months of age at treatment initiation were more likely to experience ototoxicity; long-term audiology monitoring is recommended (Qaddoumi 2012).

• Renal toxicity: Carboplatin has a limited potential for nephrotoxicity unless administered concomitantly with aminoglycosides. Use caution with concomitant administration with aminoglycosides or other nephrotoxic medications.

• Vision loss: Loss of vision (usually reversible within weeks of discontinuing) has been reported with higher-than-recommended doses.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; patients with renal dysfunction are at increased risk for bone marrow suppression.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Taxane derivatives: When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before the platinum derivatives (carboplatin, cisplatin) to limit myelosuppression and to enhance efficacy.

Special populations:

• Elderly: Patients >65 years of age are more likely to develop thrombocytopenia (severe) and peripheral neuropathy.

Other warnings/precautions:

• Dosing with Calvert formula: When calculating the carboplatin dose using the Calvert formula and an eGFR, the laboratory method used to measure serum creatinine may impact dosing. Compared to other methods, standardized isotope dilution mass spectrometry (IDMS) may underestimate serum creatinine values in patients with low creatinine values (eg, ≤0.7 mg/dL) and may overestimate GFR in patients with normal renal function. This may result in higher calculated carboplatin doses and increased toxicities. If using IDMS, the FDA recommends that clinicians consider capping estimated GFR at a maximum of 125 mL/minute to avoid potential toxicity.

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.

Monitoring Parameters

CBC (with differential and platelet count), serum electrolytes, serum creatinine and BUN, creatinine clearance, liver function tests; audiology evaluations (children <6 months); signs/symptoms of hypersensitivity reactions

Pregnancy Considerations

Carboplatin may cause fetal harm if administered during pregnancy. Women of childbearing potential should avoid becoming pregnant during treatment.

Patient Education

What is this drug used for?

• It is used to treat ovarian cancer.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Abdominal pain

• Diarrhea

• Constipation

• Hair loss

• Nausea

• Vomiting

• Mouth irritation

• Mouth sores

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting.

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Severe loss of strength and energy

• Pale skin

• Hearing impairment

• Hearing loss

• Tinnitus

• Burning or numbness feeling

• Blindness

• Severe injection site redness, burning, edema, pain or irritation

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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