Phase I/II study of gemcitabine plus mitoxantrone as salvage chemotherapy in metastatic breast cancer

Abstract

The purpose of this study was to determine the maximum-tolerated dose of gemcitabine plus mitoxantrone in women with metastatic breast cancer (MBC) and to evaluate activity and toxicity of this combination in a phase II trial. Sixty-three patients with MBC, previously treated with chemotherapy including anthracycline and/or taxanes, were treated with mitoxantrone 10 or 12 mg m À2 intravenously on day 1 plus gemcitabine in escalating doses from 600 to 1200 mg m À2 intravenously on days 1 and 8, every 3 weeks. In phase I, on 23 patients entered on study, dose-limiting toxicity occurred at the dosage of 1200 mg m À2 gemcitabine and 10 mg m À2 mitoxantrone, with three out of five patients developing grade 4 neutropenia. In phase II, with gemcitabine administered at 1000 mg m À2 and mitoxantrone at 10 mg m À2 , 12 (30%) out of 40 assessable patients responded, even if no complete response was obtained. Moreover, stable disease was observed in eight (20%) patients. The median time to treatment failure was 22 weeks (range, 2 -33), and median survival was 42 weeks (range, 2 -92). Grade 3 and 4 neutropenia were observed in 12 (30%) and one (2.5%) cases respectively; grade 3 thrombocytopenia was observed in two patients (5%), grade 2 mucositis in two patients (5%), grade 3 anaemia in two patients (5%), grade 3 alopecia in one patient (2.5%) and asymptomatic cardiotoxicity in three patients (8%), respectively. In conclusion, the doses of 10 mg m À2 (day 1) for mitoxantrone and 1000 mg m À2 for gemcitabine (days 1 -8) every 3 weeks resulted active and safe in MBC. Further investigations in less heavily pretreated patients are warranted.

Gemcitabine-induced dilated-cardiomyopathy in patient with platinum-refractory ovarian-cancer: A case report and literature review

“…[1][2][3][4] Gemcitabine is commonly used in the treatment of various solid malignancies including advanced pancreatic, bladder, breast, recurrent ovarian and nonsmall-cell lung cancer and it is also used in diffuse large B-cell lymphoma in relapsed or refractory elderly patients. [5][6][7][8][9][10][11][12] Gemcitabine is a relatively well-tolerated chemotherapeutic agent and the common adverse reactions include myelosuppression, flu-like symptoms, changes in gastrointestinal function with nausea or vomiting up to liver and kidney alterations. 13 Cardiotoxicity and dilated cardiomyopathy has not been reported during phase trial of drug development.…”

Synthesis of 2-Substituted Benzothiazole Derivatives and Their In Vitro Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells

“…Our previous study showed that benzothiazole compounds dose-dependently inhibit the proliferation of C6 (rat brain tumor) and HeLa (human uterine cancer) cell lines (25). Gemcitabine is generally used in therapy of pancreatic, bladder, breast, ovarian and non-small cell lung (26)(27)(28)(29)(30) cancer. Both compounds 4a and 4b demonstrated potent cytotoxicity towards PANC-1 cells, with IC 50 of 27±0.24 μM and 35±0.51 μM, respectively.…”

Gemcitabine and mitoxantrone in metastatic breast cancer: A phase-I-study

“…Similar results are obtained in the only other published trial that has evaluated the combination of gemcitabine and mitoxantrone in metastatic breast cancer. In this phase I/II study, a total of 63 patients were treated with gemcitabine on days 1 and 8 and mitoxantrone on day 1 in three weeks intervals [25]. DLT was grade 4 neutropenia occurring in 3 out of 5 patients at 1200 mg/m 2 gemcitabine and 10 mg/m 2 mitoxantrone.…”