Phase II randomized trial of carboplatin and gemcitabine with or without dexamethasone pre-treatment in patients with Stage IV non-small cell lung cancer.

PURPOSE: Pre-clinical and early-phase clinical studies have demonstrated that dexamethasone (DEX) administration prior to chemotherapy reduces toxicity and enhances efficacy in the treatment of cancer. We undertook a randomized, phase II multi-institutional trial to evaluate these effects in patients with Stage IV non-small cell lung cancer. METHODS: Patients were treated with carboplatin on day 1 and gemcitabine on days 1 and 8 every 21 days, for up to 6 cycles. Patients were randomized not to receive (Arm 1, n = 25) or to receive (Arm 2, n = 31) DEX orally for 4 days prior to chemotherapy on days 1 and 8. The primary endpoint was the incidence/course of grade 3 and 4 hematologic toxicity. Secondary endpoints included efficacy [response and overall survival (OS)] and evaluation of the Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, to predict survival and toxicity. RESULTS: The incidence/course of grade 3 and 4 hematologic toxicity was significantly reduced in Arm 2 (DEX) versus Arm 1 (no DEX): neutrophils = 13 versus 40 % (p = 0.009) and platelets = 23 versus 44 % (p = 0.03). Response rates and OS were higher in Arm 2 versus Arm 1: 8/31 versus 2/25 (partial response, p = ns) and 378 versus 291 days (p = ns). The GPS significantly predicted survival OS (p = 0.04) but not toxicity. CONCLUSIONS: Pre-treating patients with DEX is a safe, effective, and economic method of reducing the hematologic toxicity of carboplatin and gemcitabine. Our data suggest efficacy may also be enhanced by DEX pre-treatment.

Retreatment with bortezomib alone or in combination for patients with multiple myeloma following an initial response to bortezomib.

This clinical trial was conducted to determine the safety and efficacy of bortezomib retreatment in patients with multiple myeloma (MM) who had previously responded to bortezomib. Patients with progressive MM who had previously tolerated bortezomib as a single agent or in combination with other drugs, with a minimum of partial response (PR; >or=50% M-protein reduction) for >or=4 months, who had not received intervening MM therapy, were retreated with bortezomib (days 1, 4, 8, and 11 of a 21-day cycle) with a starting dose being the dose at which the patient ended the initial treatment. Patients were allowed to receive bortezomib on retreatment in combination with dexamethasone, thalidomide, or doxorubicin. Thirty-two patients received bortezomib retreatment (most with added dexamethasone). The median treatment-free interval (last dose of initial bortezomib treatment to first dose of retreatment) was 9.9 (range 2.5-34.0) months. The median duration of retreatment was 2.8 (<1-7.9) months; median total duration of bortezomib treatment was 6.7 (2.5-19.8) months. Based on the investigators' assessment of best response, the overall response rate (complete plus PR) was 50%. The median time from start of retreatment to progressive disease (PD) was 6.6 (95% confidence interval: 5.1-9.6) months. Thirteen patients (41%) experienced PN; bortezomib-related SAEs were reported in four patients. Retreatment with bortezomib alone or in combination is effective and well tolerated in patients with MM who have responded to their initial bortezomib treatment.

Hormone replacement therapy and survival in lung cancer in postmenopausal women in a rural population.

BACKGROUND: Hormone replacement therapy (HRT) may play a role in the development of lung cancer and subsequent survival. Results from studies exploring these issues are inconsistent. A retrospective study in a rural population was conducted to determine whether a history of HRT use is associated with survival of postmenopausal women with lung cancer. METHODS: A retrospective medical chart review of 648 postmenopausal women, diagnosed with a first primary lung cancer between 1995 and 2005, was conducted in a regional hospital in Paducah, Kentucky. History of HRT use was collected. Log-rank test and multivariate Cox regression analysis were performed to examine the effects of HRT on survival. RESULTS: The median survival for women with a history of HRT use was 16.4 months, compared with 10.5 months for women without a history of HRT use. However, this difference in survival was not statistically significant (hazard ratio, 1.09; 95% confidence interval, 0.82-1.44). Women with a history of HRT use were younger on average (64.3 years) at diagnosis than women without a history of HRT use (69.5 years, P<.01). Cigarette smoking was adversely associated with survival (P=.03), as were age (P<.01) and TNM stage (P<.01). CONCLUSIONS: In contrast to previous studies, within this population, a history of HRT use in postmenopausal lung cancer patients was not associated with decreased survival. Because most of the published studies on this issue are retrospective, the discrepant findings reflect the complexity of the role of HRT use in the survival of lung cancer patients.