Safety of BTZ retreatment for patients with low-grade peripheral neuropathy during the initial treatment.

OBJECTIVE: Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment. METHODS: Charts were reviewed from 93 patients who were retreated with a BTZ-containing regimen after previously being treated with this drug. RESULTS: Among the patients who developed PN, most patients in the study had low-grade neuropathy during the initial BTZ treatment (n = 52, 68%). The results showed no evidence of cumulative toxicity, and there was no significant difference in the incidence and severity of PN upon retreatment. Factors such as the presence of baseline PN, number of prior treatments, dose of BTZ, and comorbidities did not increase the severity of PN upon retreatment. The lapse of time between the two regimens also did not affect the severity of PN. CONCLUSION: The results suggest that retreatment with BTZ may be a feasible option, without additional risks of PN, for MM patients even with peripheral neuropathy during their initial treatment with this drug.

Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study.

BACKGROUND: Cetuximab, an immunoglobulin (Ig) G1 chimeric monoclonal antibody against the epidermal growth factor receptor, has demonstrated evidence of activity in nonsmall cell lung cancer (NSCLC). When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies. Therefore, a phase 2 study was conducted to evaluate the efficacy of the combination of cetuximab, carboplatin, and docetaxel for the treatment of advanced NSCLC. METHODS: Chemotherapy-naïve patients aged >or=18 years with stage IIIB (with effusion) or stage IV NSCLC received cetuximab (at a dose of 400 mg/m(2) on Day 1 and 250 mg/m(2) on Days 8 and 15) plus docetaxel (at a dose of 75 mg/m(2) on Day 1) and carboplatin (area under the concentration vs time curve [AUC]=6 on Day 1) every 21 days for up to 6 cycles (graded according to the American Joint Committee on Cancer Staging System). Thereafter, patients without evidence of disease progression were continued on single-agent cetuximab for a maximum of 1 year or until disease progression. The primary endpoint was response rate. RESULTS: Eighty patients were enrolled. The median number of cycles administered was 4 (range, 1-6 cycles). The objective response rate was 15.2%, with a median progression-free survival of 4.6 months and a median overall survival of 10.3 months. The salient grades 3 of 4 adverse events were neutropenia (30%), hypotension (3%), hypokalemia (4%), and hypomagnesemia (3%). Twenty-five patients received single-agent cetuximab (median duration, 12 weeks) and this was well tolerated. CONCLUSIONS: The results of this large, multicenter, phase 3 study indicate that the novel combination of cetuximab with docetaxel and carboplatin demonstrate modest anticancer activity for patients with advanced and metastatic NSCLC and has an acceptable toxicity profile.

Weekly paclitaxel, estramustine phosphate, and oral etoposide in the treatment of hormone-refractory prostate carcinoma: results of a Minnie Pearl Cancer Research Network phase II trial.

BACKGROUND: The objective of the current study was to evaluate the efficacy and toxicity of weekly paclitaxel, oral etoposide, and estramustine phosphate in the treatment of patients with advanced, hormone-refractory prostate carcinoma. METHODS: Patients with hormone-refractory prostate carcinoma who had received no more than one previous chemotherapy regimen were eligible for this trial. Forty-two patients were treated between February 1998 and March 2000. Toxicity was excessive in the first 3 patients treated (Grade 3-4 leukopenia, 3 patients; death due to sepsis, 1 patient); the remaining 39 patients received lower doses of etoposide and estramustine phosphate (paclitaxel 50 mg/m(2) as a 1-hour, intravenous infusion on Days 1, 8, 15; etoposide 50 mg orally twice daily on Days 1-10; and estramustine phosphate 280 mg orally 3 times daily on Days 1-10). Courses were repeated every 28 days. Patients were evaluated for objective and/or serologic response after two courses of treatment; responding patients continued treatment for six courses. RESULTS: Fourteen of 40 evaluable patients (35%) had either an objective response or a serologic response to treatment. The median survival for the entire group was 9.5 months, with 1-year, 2-year, and 3-year survival rates of 38%, 12%, and 10%, respectively. Neutropenia was the most common Grade 3-4 toxicity and occurred in 38% of patients (11% of courses). Thirteen patients (33%) had severe fatigue, and 2 patients had treatment-related deaths due to sepsis. CONCLUSIONS: Although the three-drug combination had activity in patients with hormone-refractory prostate carcinoma, the results did not appear any better than the results achieved with less toxic taxane/estramustine phosphate combinations. Further development of this three-drug regimen is not recommended.