ABSTRACT
BACKGROUND: Despite the advances in breast cancer care, inflammatory breast cancer (IBC) has a poor prognosis. The purpose of this study was to determine the efficacy of high-dose chemotherapy (HDCT) with thiotepa, mitoxantrone and carboplatin (TMJ regimen) in women with TNM stage IIIB IBC. PATIENTS AND METHODS: Between 1991 and 1998, twenty-eight patients with stage IIIB IBC underwent an autologous stem cell transplant after undergoing chemotherapy, surgery and/or radiation. Stem cells were collected from the bone marrow and periphery after mobilization with growth factors. Patients received thiotepa 250 mg/m2 once daily i.v. for 3 days, mitoxantrone 40 mg/m2 for 1 day and carboplatin 333 mg/m2 once daily i.v. for 3 days as the conditioning regimen for the HDCT. Radiation therapy and tamoxifen was offered to patients post HDCT if appropriate. Progression-free survival and overall survival was assessed over a 15-year period. RESULTS: At the time of last follow-up in May, 2007, sixteen patients had relapsed. The median overall survival was 49.5 months. The median progression free survival was 40 months. There were no transplant-related deaths. Mucositis and infections were the major side-effects. These results show that HDCT with the TMJ regimen is safe and effective in patients with stage IIIB IBC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/therapy , Stem Cell Transplantation/methods , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Carboplatin/administration & dosage , Carboplatin/adverse effects , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Inflammation/pathology , Middle Aged , Mitoxantrone/administration & dosage , Mitoxantrone/adverse effects , Neoadjuvant Therapy , Neoplasm Staging , Thiotepa/administration & dosage , Thiotepa/adverse effectsABSTRACT
The purpose of this study was to determine the safety of irinotecan and capecitabine in patients with advanced solid tumors. Thirty-four patients received 122 courses of irinotecan 200 to 300 mg/m(2) as an intravenous infusion during 30 minutes on day 1 and capecitabine 1,500 to 3,000 mg/d orally 12 hours apart starting on day 2 for 14 days, repeated every 21 days (one course). Three to seven patients were treated in six dose-escalation cohorts. Three of 7 (43%) patients treated with irinotecan 300 mg/m(2) and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD). Fatigue and diarrhea were the major DLTs, and other events included neutropenia, anorexia, and hand-foot syndrome. At one dose level below the MTD, none of 7 patients treated with irinotecan 275 mg/m(2), and capecitabine 2,300 mg/d (36 courses) had course 1 DLT. Grade III to IV toxicities beyond course 1 included neutropenia (11% of all courses), fatigue (3.4%) and hand-foot syndrome (3.4%). There were only two episodes of febrile grade II neutropenia. There were no toxic deaths. Transient antitumor response was noted in one patient with irinotecan and 5-fluorouracil-refractory colon cancer. The combination of irinotecan 275 mg/m(2) and capecitabine 2,300 mg/d represents a safe, favorable, and convenient outpatient regimen warranting further phase II evaluation.
