Patient-reported neuropathy and taxane-associated symptoms in a phase 3 trial of nab-paclitaxel plus carboplatin versus solvent-based paclitaxel plus carboplatin for advanced non-small-cell lung cancer.

INTRODUCTION: nab-Paclitaxel (nab-P) is approved, in the United States, in combination with carboplatin for the first-line treatment of advanced non-small-cell lung cancer, based on a randomized phase 3 trial of nab-P plus carboplatin (nab-P/C) versus solvent-based paclitaxel plus carboplatin (sb-P/C). This trial revealed a higher overall response rate (33% versus 25%; p = 0.005) and longer, but not statistically significant, overall and progression-free survival for nab-P/C versus sb-P/C. In addition, nab-P/C demonstrated lower rates of grade 3 or higher peripheral neuropathy, myalgia, arthralgia, and neutropenia but higher rates of anemia and thrombocytopenia. This report analyzes patient and physician assessment of symptoms within this trial. METHODS: Patients completed the taxane subscale of the Functional Assessment of Cancer Therapy questionnaire, which focuses on taxane toxicity, including peripheral neuropathy and neurotoxicity. Mean baseline scores and changes from baseline are reported. Physicians also graded the severity of neuropathy at each patient visit using National Cancer Institute Common Toxicity Criteria. RESULTS: Patients receiving nab-P/C reported significantly less worsening of peripheral neuropathy (p < 0.001), pain (p < 0.001), and hearing loss (p = 0.002). Patient-reported edema was similar between the two treatment arms. In agreement with patient-reported symptoms, the results of a per-treatment cycle physician assessment of peripheral neuropathy also favored nab-P/C over sb-P/C (p < 0.001). CONCLUSION: In this trial of patients receiving first-line treatment for advanced non-small-cell lung cancer, nab-P/C was associated with statistically and clinically significant reductions in patient-reported neuropathy, neuropathic pain in the hands and feet, and hearing loss compared with sb-P/C.

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial.

PURPOSE: This phase III trial compared the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin with solvent-based paclitaxel (sb-paclitaxel) plus carboplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In all, 1,052 untreated patients with stage IIIB to IV NSCLC were randomly assigned 1:1 to receive 100 mg/m(2) nab-paclitaxel weekly and carboplatin at area under the concentration-time curve (AUC) 6 once every 3 weeks (nab-PC) or 200 mg/m(2) sb-paclitaxel plus carboplatin AUC 6 once every 3 weeks (sb-PC). The primary end point was objective overall response rate (ORR). RESULTS: On the basis of independent assessment, nab-PC demonstrated a significantly higher ORR than sb-PC (33% v 25%; response rate ratio, 1.313; 95% CI, 1.082 to 1.593; P = .005) and in patients with squamous histology (41% v 24%; response rate ratio, 1.680; 95% CI, 1.271 to 2.221; P < .001). nab-PC was as effective as sb-PC in patients with nonsquamous histology (ORR, 26% v 25%; P = .808). There was an approximately 10% improvement in progression-free survival (median, 6.3 v 5.8 months; hazard ratio [HR], 0.902; 95% CI, 0.767 to 1.060; P = .214) and overall survival (OS; median, 12.1 v 11.2 months; HR, 0.922; 95% CI, 0.797 to 1.066; P = .271) in the nab-PC arm versus the sb-PC arm, respectively. Patients ≥ 70 years old and those enrolled in North America showed a significantly increased OS with nab-PC versus sb-PC. Significantly less grade ≥ 3 neuropathy, neutropenia, arthralgia, and myalgia occurred in the nab-PC arm, and less thrombocytopenia and anemia occurred in the sb-PC arm. CONCLUSION: The administration of nab-PC as first-line therapy in patients with advanced NSCLC was efficacious and resulted in a significantly improved ORR versus sb-PC, achieving the primary end point. nab-PC produced less neuropathy than sb-PC.

Weekly treatment with bortezomib for patients with recurrent or refractory multiple myeloma: a phase 2 trial of the Minnie Pearl Cancer Research Network.

BACKGROUND: The purpose of the current study was to evaluate the efficacy and toxicity of weekly bortezomib in the treatment of patients with recurrent/refractory multiple myeloma. METHODS: A total of 40 patients with multiple myeloma who had received either 1 or 2 previous treatment regimens were treated with bortezomib at a dose of 1.6 mg/m(2) intravenously for 4 consecutive weeks, followed by 1 week without treatment. Responses were measured using International Myeloma Working Group criteria. RESULTS: Twenty-two patients (55%; 95% confidence interval, 40%-70%) achieved objective responses to treatment, with a median response duration of 16 months. The median progression-free survival for all patients was 9.6 months, with a 1-year progression-free survival rate of 39%. The 1-year and 2-year overall survival rates were 75% and 51%, respectively. Weekly bortezomib was generally well tolerated; grade 3/4 (using the National Cancer Institute Common Toxicity Criteria [version 3.0]) neutropenia (13%), thrombocytopenia (20%), fatigue (15%), diarrhea (13%), and neuropathy (10%) were experienced by a minority of patients. CONCLUSIONS: In the current study, a schedule of weekly bortezomib was found to be effective and well tolerated in patients with previously treated multiple myeloma. Although the response rate and duration appear comparable to those achieved with twice-weekly bortezomib, the relative efficacy of these 2 schedules cannot be determined definitively on the basis of this phase 2 study. A weekly schedule of bortezomib is a reasonable option for patients who have logistic difficulties receiving a twice-weekly schedule, and is an attractive schedule for incorporation into combination regimens.

Community-based phase II trial of pentostatin, cyclophosphamide, and rituximab (PCR) biochemotherapy in chronic lymphocytic leukemia and small lymphocytic lymphoma.

We conducted a multicenter, community-based phase II trial of PCR biochemotherapy (pentostatin 4 mg/m2, cyclophosphamide 600 mg/m2, and rituximab 375 mg/m2) every 3 weeks for up to 6 cycles in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study was stopped after enrolling 24 patients because of diminished investigator interest after 8 patients discontinued treatment because of adverse events, and 5 others died during treatment. The median age of patients was 69 years; 11 patients were over age 70, and 71% had Rai stage III or IV disease. The response rate among the 17 evaluable patients who completed 3 cycles of therapy was 58% (35%-81%, 95% confidence interval), with 2 complete responders (both greater than 70 years of age) and 7 partial responders. No patients developed progressive disease while receiving PCR. This is the first report of a trial in CLL utilizing a combination of purine analog, alkylator, and rituximab, in which most patients were older than 65 years and had high-risk disease. PCR is active in CLL/SLL, but appears to be less active and associated with more complications in the community setting, compared to trials with younger, lower risk patients who travel to academic referral centers for treatment.

Long-term follow-up of patients treated with paclitaxel/carboplatin-based chemotherapy for advanced non-small-cell lung cancer: sequential phase II trials of the Minnie Pearl Cancer Research Network.

PURPOSE: To provide long-term follow-up on the survival of patients with advanced non-small-cell lung cancer treated with paclitaxel/carboplatin-based regimens in a multicenter, community-based setting. PATIENTS AND METHODS: Between March 1995 and April 1998, 321 patients with newly diagnosed stage IIIB or IV non-small-cell lung cancer were treated on sequential phase II trials with the following combination regimens: paclitaxel/carboplatin, paclitaxel/carboplatin/gemcitabine, and paclitaxel/carboplatin/vinorelbine. Details of these three regimens and patient populations have been previously reported. Responding and stable patients continued treatment until tumor progression or for a recommended six treatment courses. RESULTS: After a median follow-up of 58 months (minimum follow-up, 40 months), the median survival for the entire group of patients was 8.6 months, with actual 1-, 2-, and 3-year survival rates of 40%, 19%, and 7%, respectively. The actuarial 4-year survival rate for the entire group was 4%. No statistically significant differences in survival were seen among the three regimens. Administration of all three regimens was feasible in a community-based setting; however, myelosuppression and hospitalizations for treatment of neutropenia/fever were more frequent with the three-drug regimens. CONCLUSION: Paclitaxel/carboplatin-based regimens, in addition to prolonging median survival and improving 1-year survival, result in substantial improvements in the 2-year survival of patients with advanced non-small-cell lung cancer when compared retrospectively with supportive care or traditional cisplatin-based regimens. In these sequential phase II trials, we did not demonstrate any advantages of three-drug regimens when compared with paclitaxel/carboplatin. Because few patients remain alive after 4 years with any of these chemotherapy regimens, future treatment improvements will require the introduction of novel agents.