Interactions between carboplatin and Thalidomide (thalidomide)
carboplatin and thalidomide (Major Drug-Drug)
MONITOR CLOSELY: Coadministration of thalidomide with glucocorticoids and/or antineoplastic agents in the treatment of malignancy may potentiate the risk of thromboembolism. The exact mechanism is unknown but likely multifactorial. Thalidomide alone has been associated with the development of deep-vein thrombosis (DVT), and malignancy itself is also a common cause. In a study of 100 patients receiving induction chemotherapy (combinations of dexamethasone, vincristine, doxorubicin, cyclophosphamide, etoposide, and cisplatin) for multiple myeloma, the addition of thalidomide was associated with an increased incidence of DVT compared to chemotherapy without thalidomide (28% vs. 4%). Administration of thalidomide was safely resumed in 75% of patients after initiation of appropriate anticoagulation therapy. In another study, 9 of 21 (43%) patients with metastatic renal cell carcinoma (RCC) receiving gemcitabine, 5-FU, and thalidomide developed venous thromboembolism, including one case of fatal cardiac arrest. This rate is substantially higher than the 3% rate observed in a group of 125 patients previously treated at the same institution with similar regimens of gemcitabine and 5-FU but without thalidomide. It is also higher than the 9% rate (12 of 140 patients) the investigators found in a review of published data from five RCC trials that used thalidomide therapy without concomitant cytotoxic therapy. Another study found a significant association of DVT with exposure to doxorubicin in patients receiving thalidomide. Specifically, 31 of 192 (16%) multiple myeloma patients treated with DT-PACE (a regimen of dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) developed DVT, while only 1 of 40 (2.5%) did so on DCEP-T (similar to DT-PACE but without doxorubicin). The time to DVT was also significantly decreased with doxorubicin exposure. In a pooled analysis of 39 prospectively monitored clinical trials involving 1784 thalidomide-treated patients, the incidence of thromboembolism was 5% when thalidomide was used as a single agent, 13% when combined with corticosteroids (8% to 26% has been reported in individual studies with dexamethasone), and 17% when combined with chemotherapy. Among thalidomide-treated patients with multiple myeloma, thromboembolism rates ranged from a low of 1/30 among those treated with concomitant cyclophosphamide, etoposide, and cisplatin to a high of about 1/3 in those treated with doxorubicin-containing regimens.
MANAGEMENT: Close monitoring for DVT is recommended in patients who require thalidomide therapy in combination with glucocorticoids and/or cytotoxic agents. Limited data suggest that prophylactic anticoagulation with low-molecular weight heparin is effective and may be appropriate if not otherwise contraindicated. Low-dose warfarin (1 mg/day) has generally failed to demonstrate a significant protective effect, although full dose anticoagulation has shown efficacy. Aspirin may also be considered. Patients should be advised to seek medical attention if they experience symptoms that could indicate thromboembolism such as chest pain, shortness of breath, sudden loss of vision, and pain, redness or swelling in an extremity.
