TC is a chemotherapy regimen that combines Taxotere with cyclophosphamide and can be used before or after surgery to treat early-stage or localized breast cancer (breast cancer that hasn’t spread).

Combination chemotherapy, such as TC, usually works better than individual drugs because each agent works in a different way to kill cancer cells and reduce cancer spread.

What drugs are in TC chemotherapy?

The 2 drugs contained in TC are:

• Taxotere (also called docetaxel): a taxane that works by disrupting the internal structure of the cell (cytoskeleton), interfering with the ability of cancer cells to divide
• Cyclophosphamide (previous brand name Cytoxan): an alkylating agent that damages cancer cell DNA making it impossible for the cancer cells to reproduce.

The complementary mechanisms of action of these two agents means they have a powerful synergistic effect when combined because they:

• Target different cellular components (cytoskeleton vs. DNA)
• Work at different phases of the cell cycle
• Overwhelm the cancer cell’s repair mechanism
• Are more likely to overcome resistance that might develop when using either agent alone.

How is TC administered?

TC is usually given once every three weeks (21 days). It will be given intravenously (into your blood stream) by a healthcare provider in an infusion clinic or other medical facility.

Treatment may be given through a long plastic tube that goes into a large vein in your chest, such as a central line, PICC line, or a portacath, if you have one. Otherwise it may be given through a thin short tube (cannula) that goes into your arm or hand.

TC is usually given as cycles of treatment. Each cycle lasts 21 days (3 weeks).

• Day 1. Taxotere is given as a drip in your bloodstream over an hour. Cyclophosphamide is given as a slow injection or drip into your vein over about 30 minutes.

• Days 2 to 21. No treatment.

Sometimes premedication, such as antinausea treatment, is given before receiving TC.

Most people can expect to be at the clinic for 3 to 4 hours each time they receive TC chemotherapy.

When is TC used in Breast Cancer treatment?

TC is one option to treat early-stage node-negative or low-risk node-positive breast cancer that requires chemotherapy. The most common uses of TC include:

• Before surgery (this is called neoadjuvant chemotherapy)
• After surgery (this is called adjuvant chemotherapy).

Because TC does not contain an anthracycline, it may be given to breast cancer patients with heart issues, because anthracyclines (such as doxorubicin (Adriamycin) cannot be used in these patients.

When considering what chemotherapy regimen to use, healthcare providers take into account:

• How effective the regimen is compared to others. Clinical trials have determined that TC is comparable to AC (doxorubicin/cyclophosphamide) in disease-free and overall survival for early-stage breast cancer
• Particular benefits in certain subtypes: TC may offer enhanced effectiveness in certain breast cancer types, particularly HER2- negative populations
• Likely toxicities: TC has low cardiac toxicity and is used instead of AC or TAC regimens in breast cancer patients with heart issues, because it doesn’t contain an anthracycline (such as doxorubicin (Adriamycin)
• Side effect advantages: Because TC does not contain an anthracycline there is a low risk of secondary leukemias and long-term cardiac damage
• Treatment duration and complexity: TC is typically administered in 4 to 6 cycles compared to other regimens like AC-T which requires more cycles and TAC which requires more intensive supportive care and monitoring
• Patient selection factors: Higher grade cancers and younger patients may require more aggressive therapy.
• Balance of efficacy vs. toxicity: Healthcare providers take into account the risk benefit ratio of chemotherapy regimens.

How effective is TC chemotherapy?

TC chemotherapy is an effective alternative to AC (doxorubicin/cyclophosphamide) chemotherapy in breast cancer treatment. TC demonstrates comparable or superior survival outcomes while avoiding anthracycline-related cardiac toxicity, making it particularly valuable for patients with cardiac risk factors.

The results below were primarily derived from the US Oncology 9735 trial, which provided the strongest direct comparison of TC vs. AC. Subsequent meta-analyses and real-world data have generally supported these findings.

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Overall Survival (OS)

US Oncology 9735 Trial: TC showed superior overall survival compared to AC at 7-year follow-up

• TC: 87% OS rate
• AC: 82% OS rate
• Hazard Ratio: ~0.69, representing a 31% reduction in mortality risk with TC

Extended Follow-up Data: TC maintained survival advantage at longer follow-up periods, with persistent benefit observed through 10+ years

Disease-Free Survival (DFS)

Primary Endpoint Results: TC demonstrated improved DFS compared to AC

• TC: 81% DFS rate at 7 years
• AC: 75% DFS rate at 7 years
• Hazard Ratio: ~0.74, representing a 26% reduction in recurrence or death risk

Subset Analysis: DFS benefit was observed across most major subgroups, including both node-positive and node-negative patients

Recurrence Reduction

• Distant Recurrence: TC showed approximately 25-30% relative reduction in distant recurrence compared to AC
• Local-Regional Recurrence: Similar trend fevering TC with approximately 20-25% relative reduction
• Site-Specific Recurrence: TC appeared particularly effective at reducing bone and visceral metastases compared to AC

Key Considerations

• The survival and recurrence advantages of TC over AC appeared more pronounced in certain subgroups, particularly women over 50 years of age
• Benefits were consistent across hormone receptor status categories, though magnitude varied
• Modern analyses suggest the differences may be partially attributed to the specific taxane (docetaxel) in TC rather than solely the absence of anthracycline

What are the common side effects of TC?

Most side effects from TC are temporary and manageable.

The most common side effects of TC are:

• Hair loss
• Fatigue
• Irregular periods
• Low blood counts (low platelets/neutrophils)
• Nail changes
• Muscle/joint aches
• Numbness/tingling in the hands and feet
• Reflux or heartburn
• Mouth sores
• Taste changes.

Less common side effects of TC are:

• Swelling in the arms or legs
• Diarrhea
• Constipation
• Nausea
• Vomiting
• Fever
• Infection
• Mild infusion reactions.

Rarely, TC may cause bladder damage, secondary blood cancers (such as leukemia), or lung inflammation.

Managing side effects from TC

Allergic reactions

• Premedicate with an antihistamine and corticosteroid to reduce risk.

Hair loss

• Consider cold caps to cool the scalp during chemotherapy and reduce the amount of chemotherapy reaching the hair follicles.

Infection

• Ask your healthcare provider about pegfilgrastim or biosimilar 24-48 hours after chemotherapy to reduce infection risk.
• Wash your hands frequently, avoid large crowds, animal waste, or people who are sick.

Swelling, nausea, and vomiting

• Dexamethasone taken before, during, and after chemo.

Nausea and vomiting

• Antiemetic before chemotherapy.
• Antiemetic to take home.

Diarrhea

• Loperamide to reduce the frequency of your bowel movements.

Constipation

• Laxatives to improve how frequently you go to the toilet.

Peripheral neuropathy

• Protect hands/feet from extreme cold.
• Wear comfortable nonslip shoes.

Fertility

• Talk to your healthcare provider about egg harvesting or sperm banking before you start treatment.

Important considerations during treatment

• Avoid immunizations with live vaccines (measles, mumps, BCG) while you are having treatment and for up to 12 months afterwards. Ensure you are up to date with you vaccinations before you start treatment.
• Do not become pregnant while having treatment with TC because it may harm your unborn baby. Use effective contraception while you are having treatment and for a year afterwards.
• Reduce your risk of infection by washing your hands frequently and staying away from sick people or large crowds.
• Do not breastfeed while having TC.

Blood monitoring required before each cycle.

• A complete blood count and comprehensive metabolic panel is typically required before the start of each TC cycle to ensure your blood counts have recovered sufficiently before the next treatment.
• TC carries a high risk of febrile neutropenia. Your healthcare provide may consider use of pegfilgrastim to reduce this risk.
• Keep all your appointments and tell your healthcare team about any side effects you may have.

References

• Chemotherapy for Breast Cancer. American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/treatment/chemotherapy-for-breast-cancer.html
• TC Chemotherapy teaching. Mass General Cancer Center. https://www.massgeneral.org/assets/mgh/pdf/cancer-center/breast-cancer/chemotherapy-regimen-tc.pdf
• TC Protocol: Taxotere + Cytoxan. BreastCancer.org https://www.breastcancer.org/drugs/TC-chemo
• Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. doi: 10.1200/JCO.2008.18.4028. Epub 2009 Feb 9. PMID: 19204201.
• Caparica R, Bruzzone M, Poggio F, Ceppi M, de Azambuja E, Lambertini M. Anthracycline and taxane-based chemotherapy versus docetaxel and cyclophosphamide in the adjuvant treatment of HER2-negative breast cancer patients: a systematic review and meta-analysis of randomized controlled trials. Breast Cancer Res Treat. 2019 Feb;174(1):27-37. doi: 10.1007/s10549-018-5055-9. Epub 2018 Nov 21. PMID: 30465156.

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