Effective Salvage Therapy with Carboplatin/Mitomycin C in Metastatic Breast Cancer

Abstract

Background: Alternative and effective drug regimens in patients with metastatic breast cancer progressing after adriamycin- and taxoid-containing regimens are urgently needed. Patients and Methods: In a phase II trial, 43 heavily pretreated patients with metastatic breast cancer were treated with both carboplatin 200 mg/m² i.v. and mitomycin C 10 mg/m² i.v. on day 1 every 4 weeks. In case of granulocytopenia or thrombocytopenia below grade 3 according to NCI-CTC, the carboplatin dosage was escalated to 300, 400, and 450 mg/m² in the next treatment cycle. Results: During the first 3 cycles the dose intensity of carboplatin could be increased from a mean of 50 to 74 mg/m²/week. Beyond this value the carboplatin dose intensity decreased because of hematotoxicity. Based on an intention-to-treat analysis, 9 of 43 patients responded to therapy (21%; 95% CI = 10.04–36.04) including 2 complete and 7 partial responses. 15 patients had no change, 13 progressed, and 6 patients were considered nonevaluable. The median time to progression was 3 (range 0–12) months. NCI-CTC grade 3 or 4 granulocytopenia was observed in 14 patients, grade 3 or 4 thrombocytopenia occurred in 32, grade 3 infections in 3, grade 3 hemorrhage in 1, and grade 3 cardiac dysrhythmias in 1 of the patients. Conclusions: In anthracycline/ taxoid-pretreated patients, salvage treatment with a combination of carboplatin and mitomycin C seems to be effective and associated with foreseeable toxicity. Based on our results with an intraindividual dose escalation of carboplatin, a dosage of 300 mg/m² in combination with mitomycin C 10 mg/m² every 4 weeks seems to represent a recommendable starting dose for future studies.

Mitomycin C in Patients with Gynecological Malignancies

“…Another very recent area of application for MMC is in patients with triple-negative breast carcinoma. Thereisastrongneedforalternativetherapeuticoptions,especiallyforpatientswithprogressoftherecommendedfirstlinetherapypaclitaxel/bevacizumab [1].MMC(e.g.incombinationwithcarboplatin)maydevelopoverthenextfewyears tobecomeavaluableoptionhere [44,45,51].Furtherphase IIIstudiesarenecessarytoprovethementionedresults.The treatments described can usually be carried out on an outpatientbasis.Whenthetoxicityprofilesareacceptable,avery goodqualityoflifeismaintained.Inthelastfewyears,alarge numberofnewanti-cancerdrugshavebeenintroducedinthe clinical setting, most of them with a specific intra-or extracellular target [2]. But also in times of a more 'biological therapy', MMC will not be replaced completely by these drugs,becauseonlyasmallpartofthemhasasuperiorefficacyincomparisontoconventionalchemotherapyagentslike MMC.SoMMCwill-togetherwithotherconventionalcytotoxicdrugs-retainitsroleinthesalvagetreatmentofMBC.…”

Fluorouracil and Mitomycin: An Option for Metastatic Breast Cancer

“…Further promising results have been reported in recent studies of combinations of mitomycin C with agents such as docetaxel or carboplatin [9,10].…”