A phase II trial of neoadjuvant gemcitabine, epirubicin, and docetaxel as primary treatment of patients with locally advanced or inflammatory breast cancer.

BACKGROUND: Three-drug regimens containing gemcitabine, an anthracycline, and a taxane produce response rates of 70%-90% in patients with metastatic breast cancer (MBC) although accompanied by considerable hematologic toxicity. We explored the combination of gemcitabine/epirubicin/docetaxel as neoadjuvant therapy. Docetaxel was administered weekly to decrease myelosuppression. PATIENTS AND METHODS: A total of 110 patients with locally advanced or inflammatory breast cancer received neoadjuvant gemcitabine 800 mg/m2 intravenously (I.V.) days 1 and 8, epirubicin 75 mg/m2 I.V. day 1, and docetaxel 30 mg/m2 I.V. days 1 and 8, repeated every 21 days for 4 cycles. Then patients had either mastectomy or breast conservation surgery, and pathologic treatment responses were assessed. After surgery, 4 cycles of adjuvant gemcitabine 1000 mg/m2 I.V. days 1 and 8 and docetaxel 35 mg/m2 I.V. days 1 and 8 were administered at 21-day intervals. After patients completed chemotherapy, locoregional radiation therapy and/or anti-estrogen therapy was administered per standard guidelines. RESULTS: Treatment with 4 cycles of neoadjuvant gemcitabine, epirubicin, and weekly docetaxel resulted in an objective response in 79 of 110 patients enrolled (72%; 95% CI, 63-80%). Twenty of 103 patients (19%) who had surgery had pathologic complete response (pCR). Moderate hematologic toxicity was evident during neoadjuvant therapy, with grade 3/4 neutropenia in 41% and febrile neutropenia in 11% of the patients. Protocol-specified dose modifications were required in 35% of the patients, and 58% of the patients used myeloid growth factors. CONCLUSION: The pCR rate of 19% achieved with gemcitabine, epirubicin, and weekly docetaxel confirms previous reports with similar 3-drug regimens. The use of a weekly schedule of docetaxel did not appear to reduce the incidence of grade 3/4 hematologic toxicity.

Irinotecan, carboplatin, and imatinib in untreated extensive-stage small-cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.

INTRODUCTION: The tyrosine kinase KIT has variable expression in small-cell lung cancer (SCLC) and may be a prognostic factor. Imatinib targets KIT expression, providing rationale for studying its role in combination with chemotherapy in SCLC in a multicenter phase II trial. METHODS: Patients with untreated extensive-stage SCLC received carboplatin area under the concentration-time curve of 4 on day 1; irinotecan 60 mg/m2 on days 1, 8, and 15; and imatinib 600 mg/day. Treatment cycles were 28 days. Patients remained on imatinib until progressive disease or significant toxicity. RESULTS: Between September 2002 and May 2004, 68 patients were enrolled in this multicenter trial. Median age was 60 years (range, 37-81). The objective response rate was 66% (95% confidence interval: 54%-76%). Median progression-free survival was 5.4 months (95% CI: 4.3-6.0 months). Median overall survival was 8.4 months (95% CI: 6.3-10.5 months). Thirty-five percent of patients were alive at 1 year. Grade 3/4 hematologic toxicity included neutropenia (43%), anemia (16%), and thrombocytopenia (9%). Grade 3 nonhematologic toxicity included diarrhea (19%), fatigue (24%), and nausea (26%). Forty-eight of 56 patients (86%) with available tumor specimens had KIT expression detected. KIT expression did not appear to correlate with progression-free survival or overall survival in a retrospective analysis. CONCLUSIONS: Irinotecan, carboplatin, and imatinib is a safe and generally well-tolerated regimen in patients with SCLC. However, the addition of imatinib did not improve results from those expected with chemotherapy alone.

Phase II study of gemcitabine and cisplatin in patients with previously untreated extensive stage small cell lung cancer: Southwest Oncology Group Study 9718.

BACKGROUND: This phase II study (S9718) evaluated the antineoplastic activity and tolerability of the combination of gemcitabine and cisplatin in previously untreated patients with extensive stage small cell lung cancer (ES-SCLC). METHODS: Chemonaive patients with ES-SCLC, received gemcitabine 1250 mg/m intravenously (IV) over 30 minutes on days 1 and 8 and cisplatin 75 mg/m IV over 30 to 60 minutes on day 1. Treatments were repeated every 21 days for a maximum of six cycles. RESULTS: A total of 88 patients were enrolled in the study; seven patients were not eligible and one did not receive treatment; 80 patients were fully assessable for survival, response, and toxicity. Objective response was observed in 42 patients (53%; 95% confidence interval [CI]: 41%-64%) with two patients (3%; 95% CI: 0%-8%) achieving a complete response. Median PFS was 5 months (CI, 4.2-5.9 months), and median overall survival was 8.8 months (95% CI: 7.8-9.5 months). The 1- and 2-year survival rates were 27.5% (95% CI: 17.7%-37.3%) and 4% (95% CI: 0%-8%), respectively. The most common toxicity was neutropenia. Grade 3 and 4 neutropenia was noted in 17 (21%) and 17 (21%) patients, respectively. Two patients developed febrile neutropenia, with subsequent full recovery. Twenty-one patients (23%) developed grade 3 thrombocytopenia. Grade 4 thrombocytopenia was seen in only one patient. The most common nonhematologic toxicities included grade 3 and 4 vomiting in 12 (21%) patients and fatigue in nine (10%) patients. Two patients (3%) died of respiratory infections while on treatment. CONCLUSION: The combination of gemcitabine and cisplatin is an active and reasonably well tolerated regimen for the treatment of ES-SCLC. It does not appear to offer any compelling advantages over other commonly used two drug regimens in this disease.