A phase II open-label trial of bortezomib in patients with multiple myeloma who have undergone an autologous peripheral blood stem cell transplant and failed to achieve a complete response.

BACKGROUND: A majority of multiple myeloma (MM) patients fail to achieve complete response (CR) to peripheral blood stem cell transplantation (PBSCT); effective options following autologous transplantation are needed. Bortezomib (B) is active against MM. This study was conducted to determine the feasibility, safety, tolerability, and efficacy of B following high-dose melphalan therapy and PBSCT. Methods Fifty patients enrolled (48 evaluable) and 49 were treated (safety population). TREATMENT: 4 cycles B 1.3 mg/m(2) Days 1, 4, 8, and 11/21-days; 4 additional cycles were permitted for stable or responding patients. Results Median age was 55 years (range, 38-73), 68% male, 64% ECOG PS = 0, 44% Durie-Salmon Stage IIIA prior to induction, 42% had symptomatic IgG MM; 74% had prior single transplant (26% tandem). Responses post-transplant: 70% PRs, 18% MRs. A median of 4 cycles (range, 2-8) of B were administered. Responses: CR 8%, uCR 2%, PR 23%, uPR 19%, MR 10%, and no change 35%; median time-to-treatment failure (TTF) was 6.2 months (range, 1.0-19.4). Three deaths occurred (n = 1 sepsis, n = 2 disease progression). Grade 3-4 treatment-related toxicities included: thrombocytopenia, neuropathy (14%, each); asthenia, neutropenia (10%, each); and nausea (4%). Twelve patients (24%) discontinued treatment due to toxicity and 30 patients (60%) completed the study; 20 patients started new treatment (median 5.8 months [range, 1.5-20.3]). CONCLUSIONS: The study closed early due to widespread availability of B, and the lack of B-naïve patients. Bortezomib monotherapy after melphalan and autologous PBSCT was feasible, safe and well-tolerated (toxicities were manageable), but failed to produce the hypothesized response rates.

Randomized phase II study of cetuximab and bevacizumab in combination with two regimens of paclitaxel and carboplatin in chemonaive patients with stage IIIB/IV non-small-cell lung cancer.

INTRODUCTION: We conducted a phase II study of dual-agent monoclonal antibody therapy consisting of cetuximab and bevacizumab in combination with paclitaxel and carboplatin chemotherapy in non-small-cell lung cancer. METHODS: Patients with stage IIIB/IV nonsquamous non-small-cell lung cancer randomly received cetuximab (400 mg/m initially, 250 mg/m weekly thereafter) plus bevacizumab (15 mg/kg) for six cycles combined with paclitaxel (200 mg/m) and carboplatin (area under the curve 6) for either six cycles (six-cycle arm) or the first three cycles (three-cycle arm) (one cycle = 3 weeks). The primary objective was progression-free survival (PFS), estimated separately for each treatment arm. RESULTS: In 121 patients, the median PFS was 6.05 months (95% confidence interval [CI]: 5.65, 7.03) in the six-cycle arm and 4.50 months (95% CI: 4.01, 5.42) in the three-cycle arm. Respective median overall survival times were 12.06 months (95% CI: 9.40, 19.25) and 11.63 months (95% CI: 6.64, 17.61). The tumor response rate was 51.7% (95% CI: 39.0%, 64.3%) and 44.3% (95% CI: 31.8%, 56.7%) in the six-cycle and three-cycle arms, respectively, with corresponding median response durations of 4.86 months (95% CI: 4.30, 7.16) and 3.94 months (95% CI: 2.92, 4.47). Quality of life was consistent across arms. Cetuximab-related grade 3/4 events in greater than 5% of patients (six-cycle arm, three-cycle arm) were dermatitis acneiform (6.9%; 8.6%) and fatigue (13.8%; 5.2%). Three patients died during the study from drug-related adverse events (one in the six-cycle arm and two in the three-cycle arm). CONCLUSIONS: Both the regimens showed expected PFS and numerically comparable overall survival. Quality of life was similar in the two arms, and both the regimens were well tolerated.

A randomized, multicenter, open-label comparison of the antiemetic efficacy of dolasetron versus ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy.

This study assessed the efficacy and safety of dolasetron compared with ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy followed by peripheral blood stem cell support. Twenty centers randomized 197 patients to receive dolasetron 100 mg intravenously (I.V.) followed 8-12 hours later by a single oral dose of dolasetron 100 mg or ondansetron 32 mg I.V., followed 8-12 hours later by a single oral dose of ondansetron 8 mg during high-dose chemotherapy (HDC) regimens for breast cancer (n = 96; 48.7%), non-Hodgkin's lymphoma (n = 83; 42.1%), or Hodgkin's disease (n = 18; 9.1%). All patients received a daily I.V. bolus of dexamethasone 10 mg with study antiemetic agents and a continuous infusion of diphenhydramine, lorazepam, and dexamethasone (ie, BAD pump) throughout the course of the study, with patient-controlled on-demand bolus doses as needed. After completing a daily diary of emetic episodes and rescue medication use, 164 of 197 patients were evaluable. Total plus complete responses (no emesis, no nausea, no rescue) over the entire study period were achieved in 45.7% and 46.9% of patients on the dolasetron and ondansetron arms, respectively. Dolasetron and ondansetron were well-tolerated. This study demonstrates that dolasetron and ondansetron are equally safe and effective in the prevention of nausea and vomiting associated with HDC (P = 0.955).

Impaired gastric slow wave rhythmicity in patients after bone marrow or stem cell transplant.

Patients after bone marrow or stem cell transplant often develop gastrointestinal symptoms. The aim of this study was to investigate possible impairment of gastric myoelectrical activity in these patients. The study was performed in 15 patients who had had bone marrow or stem cell transplant and 13 healthy subjects. Gastric myoelectrical activity was assessed using electrogastrography. The electrogastrogram (EGG) was made for 30 min in the fasting state and 60 min after a test meal (475 kcal; turkey sandwich). Overall and minute-by-minute spectral analyses were performed to derive various parameters of the EGG. Compared with the healthy controls, the patients showed a significantly higher percentage of arrhythmia (no obvious rhythmicity observed in the EGG) in both fasting (17.6 +/- 3.8% vs 7.1 +/- 2.17%, P < 0.02) and fed (11.4 +/- 2.65% vs 4.19 +/- 1.04%, P < 0.02) state. The patients showed a significantly higher instability coefficient of the dominant frequency in the fasting state than in the controls (0.51 +/- 0.06 vs 0.29 +/- 0.18, P < 0.008). The total average symptom score was 3.93 +/- 0.84 in the patients and 0 in the controls, and a relatively weak but significant correlation was found between the symptom scores and the percentage of arrhythmia in the patients in fed state (r = 0.69, P < 0.02). It was concluded that patients with bone marrow or stem cell transplant have excessive arrhythmia that is correlated with their dyspeptic symptoms.