A Trial of Doxil and Multiday Vinorelbine in Patients With Metastatic Breast Cancer

PROTOCOL SUMMARY Study design: Phase II trial of monthly Doxil® and vinorelbine on day 1 and 2 in women with metastatic breast cancer. Treatment plan: Patients will continue therapy, until they have unacceptable toxicity or disease progression. Primary endpoint: Response rate Secondary endpoints: Time to progression, overall survival and toxicity. Additional study objectives: Evaluation of treatment-related dyspnea, with measurement of pulse oximetry during and after drug administration, and rigorous study of patients who experience dyspnea. Palmar-plantar erythrodysesthesia (PPE) will be treated with one of 2 randomly assigned topical salves, measuring duration and severity of symptoms. Eligibility: Women who have had prior chemotherapy in the adjuvant or metastatic setting, or both, up to 3 prior regimens. Patients having more than one prior regimen for metastatic disease must have a performance status of 0 or 1; others may have 0-2. No prior Doxil® or vinorelbine therapy. Patients are ineligible if prior anthracycline dose is greater than 400 mg/m2, or if they have primary anthracycline-refractory disease, with disease progression during treatment or with relapse/recurrence within 6 months after last dose of anthracycline. Patients must have normal neurologic, hematologic, renal and hepatic functional parameters. Asymptomatic brain metastases are permissible. Treatment plan: Doxil® 40 mg/m2 IV infusion over 60 minutes on day 1 Vinorelbine 15 mg/m2 IV over 6 minutes on days 1 and 2 Dexamethasone 4 mg IV or 8 mg po (Doxil® pretreatment) Heparin 5000 U IV (Vinorelbine pretreatment) Pyridoxine (vitamin B6) 200 mg po qd Repeat every 28 days. Supportive measures: For anemia (hematocrit \< 35): Procrit® 40,000 U q wk For neutropenia (ANC \< 1,000/mm3 ): Prophylactic antibiotics (Cipro® or Septra®) For all cycles after neutropenic fever/infection or grade 3-4 stomatitis: Prophylactic Neulasta® 6 mg SQ on day 3 (This intervention may be adopted for all patients, all cycles, if 2 of the first 4 patients enrolled need it.) For PPE: randomize between 2 topical salves and document duration and severity of sx Dose adjustments: Subsequent cycles are given on day 29 or after recovery or to grade 0-1 toxicity, with no more than 3 weeks delay. Reduce dose of both drugs by 25% if grade 3 or 4 stomatitis or palmar-plantar or grade 4 thrombocytopenia. Reduce dose of Doxil® ONLY by 50-75% if abnormal bilirubin, alkaline phosphatase and/or ALT, AST (appendix 14.3)