First-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer

Summary

The purpose of this study was to evaluate the efficacy and tolerance of combined treatment with docetaxel–cisplatin as first-line chemotherapy in patients with metastatic breast cancer (MBC). Consecutive eligible chemonaive patients received docetaxel 75 mg/m² on day 1 and cisplatin 75 mg/m² on day 2 every 3 weeks for 6 cycles, with prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on days 4–11. Thirty-two patients (64%) had received prior adjuvant chemotherapy; these included 16 (32%) who had received anthracyclines. In 50 evaluable patients with a median age (range) of 56 (31–72) years, the overall response rate was 68% (95% CI, 55–81%), with 7 (14%) complete and 27 (54%) partial responses. Stable and progressive disease was observed in 10 (20%), and 6 (12%) patients, respectively. The median duration of response was 10 months, and the median time to progression was 39 weeks. Grade 3/4 hematological toxicity included—neutropenia in 9 patients (18%), anemia in 2 (4%) and thrombocytopenia in 1 (2%). One patient (2%) with febrile neutropenia required hospitalization. Grade 3/4 nonhematological toxicities included nausea/vomiting in 18%, nephrotoxicity in 14%, asthenia (4%), and neurotoxicity (2%). Toxicity was common in older patients (>56 years). There were no treatment-related deaths. A combination of docetaxel–cisplatin with rHuG-CSF support is well tolerated and effective as first-line chemotherapy in MBC.

Introduction

Even after adequate loco-regional treatment and systemic adjuvant polychemotherapy at the time of diagnosis, metastatic relapses occur in 40% of patients with breast cancer.¹ The increasingly frequent use of anthracyclines in adjuvant treatment has led to a limitation of their use in relapsing patients. A need has therefore emerged for active nonanthracycline-containing regimens. Among the novel chemotherapeutic drugs introduced in the last decade, docetaxel (DOC) has emerged as a promising compound with remarkable activity when given alone as first-line treatment.2, 3, 4, 5

Cisplatin (CDDP) as a single agent is very active as first-line treatment in metastatic breast cancer (MBC), with response rates of 47–54%.6, 7, 8 On the basis of the reports in the relatively small literature, it can be argued that CDDP is the third most active agent in this disease, after taxanes and doxorubicin, but the relative severity of toxicity limits its use in routine clinical practice.⁹

Like others, we have shown that regimens combining CDDP with vinorelbine, when used as second-line treatment in MBC, are well tolerated and effective in patients who have been pretreated with anthracyclines¹⁰ and docetaxel.¹¹ In vitro studies suggest a powerful synergy between platinum complexes and docetaxel and between platinum complexes and trastuzumab.¹² These data, together with the widespread use of anthracyclines in adjuvant therapy suggest one possible role for platinum-containing regimens early in the treatment of MBC. Docetaxel is widely used after failure with anthracyclines, and preliminary data indicate a high antitumor activity of combined DOC/CDDP in this group of patients. The regimen has been found to be very active in the neoadjuvant setting, with acceptable toxicity.¹³

Based on preliminary data,14, 15, 16, 17 this study assessed the antitumor activity and tolerance of DOC 75 mg/m² on day 1, followed by CDDP 75 mg/m² on day 2, as first-line treatment in chemonaive patients with MBC. Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) was given prophylactically against neutropenia because severe neutropenia has been observed in earlier studies.¹⁸