BioOncology Watch Timely Information for Practicing Physicians
september 2003 METASTATIC BREAST CANCER Trastuzumab and vinorelbine as first-line therapy. Although trastuzumab-based therapy has become a standard treatment for patients with HER2-positive metastatic breast cancer, it can be cardiotoxic, especially when combined with anthracyclines. Vinorelbine is not associated with cardiotoxicity and has exhibited synergistic activity with trastuzumab in preclinical models of HER2-overexpressing breast cancer cell lines. Harold Burstein et al performed a multicenter phase II study in which 54 women with HER2- positive (immunohistochemistry 3+ positive or FISH-positive) metastatic breast cancer received trastuzumab (4 mg/kg followed by 2 mg/kg intravenously [i.v.] weekly) plus vinorelbine (25 mg/m^2i.v. weekly). Only 2 patients developed > grade 1 cardiotoxicity (one patient with symptomatic heart failure). Both of these patients had a left ventricular ejection fraction < 50% at week 16. The response rate was 68% and the 1-year progression-free survival rate was 38%. These data suggest that the combination of trastuzumab and vinorelbine is safe and effective first-line therapy for patients with metastatic breast cancer. (Bursein HJ, et al. J Clin Oncol 2003;21:2889-2895) LEUKEMIA Priming with granulocyte colony-stimulating factor (G-CSF) in acute myeloid leukemia (AML). In vitro studies have shown that simultaneous exposure of leukemic cells to chemotherapy and growth factors increases the susceptibility of malignant cells to cell-cycle-specific chemotherapy. These findings led Bob Löwenberg and colleagues to conduct a multicenter study in which 321 previously untreated AML patients were randomized to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with or without G-CSF. G-CSF was given subcutaneously or intravenously at a dose of 150 ug/m^2/day beginning one day before chemotherapy and continuing until the last day of cycles 1 and 2. Response rates were similar in the 2 treatment groups. However, after a median follow-up of 55 months, patients in the G-CSF group had a higher 4-year disease-free survival rate (42% vs. 33%). Although overall survival was not improved, the 4-year overall survival rate for patients with standard-risk AML (72% of the patients) treated with G-CSF was greater than that for those not treated with G-CSF (45% vs. 35%). These findings indicate that priming of leukemic cells with G-CSF enhances the efficacy of chemotherapy in AML patients. In an accompanying editorial, Charles Schiffer cautions that previous randomized studies of GM-CSF priming have failed to show a benefit in patients with AML and that priming with growth factors may increase the sensitivity of normal precursor hematopoietic cells to chemotherapy. He suggests that further confirmatory studies in younger patients with standard-risk AML are needed. (Löwenberg B, et al. N Engl J Med 2003;349:743-752 and Schiffer CA. N Engl J Med 2003;349:727-729) Rituximab treatment of relapsed patients with hairy cell leukemia (HCL). HCL is a rare B-cell lymphoproliferative disorder that expresses CD20. Jorge Nieva and coworkers observed that rituximab treatment (375 mg/m^2 weekly for 4 weeks) of 24 HCL patients who had relapsed after cladribine therapy resulted in a response rate of 25% (6 patients; 3 patients had complete remissions). With a median follow-up of 14.6 months, 2 responders had relapsed and the median time to relapse had not been reached. These findings of moderate activity indicate that further investigations of rituximab, either combined with other active agents or given by an alternate schedule, in cladribine-failed HCL patients are warranted. (Nieva J, et al. Blood 2003;102:810-813) NON-HODGKIN'S LYMPHONA (NHL) Phase I/II trial of epratuzumab. The CD22 antigen is expressed in at least 60% to 80% of B-cell malignancies tested and represents a potential therapeutic target for lymphoma. John Leonard and colleagues conducted a single-center, phase I/II, dose-escalation study of epratuzumab (Immunomedics, Inc.), an anti-CD22 humanized monoclonal antibody, in patients with indolent NHL who had progressive disease after at least one regimen of standard chemotherapy. Epratuzumab was administered intravenously at 120 to 1,000 mg/m^2 over 30-60 minutes weekly for 4 treatments to 55 patients without dose-limiting toxicity. Overall, 9 (18%; 95% CI: 8%-31%) patients achieved an objective response (3 patients with complete responses). All responses occurred in patients with follicular NHL. Forty-three percent and 27% of follicular NHL patients treated at the 360 and 480 mg/m^2 dose levels, respectively, responded. The median duration of objective response was 79.3 weeks and the median time to progression for responders was 86.6 weeks. These results demonstrate that epratuzumab has activity against follicular NHL and that further studies of the 360 mg/m^2/ week dosing schedule are warranted. (Leonard JP, et al. J Clin Oncol 2003;21;3051-3059) CHOP followed by tositumomab/iodine-131 tositumomab. Oliver Press et al from the Southwest Oncology Group (SWOG) gave 90 previously untreated follicular NHL patients 6 cycles of CHOP followed 4 to 8 weeks later by tositumomab/iodine-131 tositumomab (75 cGy whole-body dose of iodine-131; SWOG Protocol 9911). Among 47 evaluable patients, 27 (57%) patients improved their remission status with tositumomab/iodine-131 tositumomab treatment after CHOP chemotherapy. The overall response rate to the entire treatment regimen was 90% (67% complete responses). With a median follow-up of 2.3 years, the 2-year progression-free and overall survival rates were 81% and 97%, respectively. These favorable data have led to a phase III, randomized study conducted by SWOG and the Cancer and Leukemia Group B comparing CHOP-rituximab and CHOP-tositumomab/iodine-131 tositumomab therapies in patients with newly diagnosed follicular NHL (S0016). (Press OW, et al. Blood 2003;102:1606-1612)
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