Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial.

BACKGROUND: Available preclinical and phase 2 clinical data suggest that the addition of cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), to chemotherapy might improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to assess whether the addition of cetuximab to chemotherapy improved progression-free survival in patients with recurrent or progressive NSCLC after platinum-based therapy. METHODS: In this unmasked, open-label randomised phase 3 trial we enrolled patients with metastatic, unresectable, or locally advanced NSCLC from 121 sites in Canada and the USA. Eligible patients were those aged 18 years or older who had experienced progressive disease during or after one previous platinum-based regimen. Initially, patients were randomly assigned to receive either pemetrexed (500 mg/m(2)) or docetaxel (75 mg/m(2)) and then randomly assigned within each group to receive their chemotherapy with or without cetuximab (400 mg/m(2) at first dose and 250 mg/m(2) weekly thereafter) until disease progression or unacceptable toxicity. However, after a change in the standard of care, investigators chose whether to treat with pemetrexed or docetaxel on a patient-by-patient basis. The primary analysis was changed to compare progression-free survival with cetuximab plus pemetrexed versus pemetrexed, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00095199. FINDINGS: Between Jan 10, 2005, and Feb 10, 2010, we enrolled 939 patients; data for one patient was accidentally discarded. Of the remaining 938 patients, 605 received pemetrexed (301 patients with cetuximab and 304 alone) and 333 received docetaxel (167 in combination with cetuximab and 166 alone). Median progression-free survival with cetuximab plus pemetrexed was 2·9 months (95% CI 2·7-3·2) versus 2·8 months (2·5-3·3) with pemetrexed (HR 1·03, 95% CI 0·87-1·21; p=0·76). The most common grade 3-4 adverse events with cetuximab plus pemetrexed were fatigue (33 [11%] of 292 patients), acneiform rash (31 [11%]), dyspnoea (29 [10%]), and decreased neutrophil count (28 [10%]), and with pemetrexed alone were dyspnoea (35 [12%] of 289 patients), decreased neutrophil count (26 [9%]), and fatigue (23 [8%]). A significantly higher proportion of patients in the cetuximab plus pemetrexed group (119 [41%] of 292 patients) experienced at least one serious adverse event than those patients in the pemetrexed group (85 [29%] of 289 patients; p=0·0054). Nine (3%) of 292 treated patients in the cetuximab and pemetrexed group died of adverse events compared with five (2%) of 289 treated patients in the pemetrexed alone group. INTERPRETATION: The use of cetuximab is not recommended in combination with chemotherapy in patients previously treated with platinum-based therapy. FUNDING: Eli Lilly and Company and ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company.

Phase II study of low-dose docetaxel/estramustine in elderly patients or patients aged 18-74 years with hormone-refractory prostate cancer.

PURPOSE: Chemotherapy is often poorly tolerated in elderly patients or patients with poor performance status. This trial was designed to determine whether low-dose weekly docetaxel/estramustine was efficacious with acceptable toxicity. PATIENTS AND METHODS: Dexamethasone was administered as premedication. Subjects received docetaxel 25 mg/m2 intravenously on days 2, 9, and 16 and estramustine 140 mg orally twice daily on days 1-3, 8-10, and 15-17. Cycles were 28 days. Participants received < or = 6 cycles unless progression or intolerable toxicity occurred. RESULTS: Fifty-eight subjects were enrolled at 31 sites in the US Oncology Network. Median age was 78 years (range, 64-92 years); performance status scores (0, 1, 2, and 3) were 36%, 38%, 24%, and 2%, respectively; 55 subjects received > or = 1 cycle of treatment; and 4 participants were nonevaluable because they completed < 2 cycles. Among the 56 treated subjects, 38 (68%) had a decreased prostate-specific antigen level (> or = 50% compared with baseline level and maintained for 4 weeks). There were 40 subjects with measurable tumor(s). Responses, assessed using Response Evaluation Criteria in Solid Tumors, were 1 complete response (2.5%), 7 partial responses (17.5%), 26 stable diseases (65%), and 6 progressive diseases (15%). At 1 year, 17% of participants were progression free; median progression-free survival was 5.3 months (range, 1-14.5 months); estimated 1-year survival was 65%. There were no grade 4 treatment-related events. Grade 3 treatment-related events included fatigue/asthenia (11%) and arrhythmia, dehydration, cerebral ischemia, thrombocytopenia, and dyspnea (4% each). There was 1 treatment-related death (acute respiratory distress syndrome). CONCLUSION: These findings suggest that elderly men with advanced-stage prostate cancer tolerate this regimen, with significant responses and prolonged progression-free survival. These patients should not be excluded from chemotherapeutic interventions based on age alone.

Comparison of menopausal symptoms during the first year of adjuvant therapy with either exemestane or tamoxifen in early breast cancer: report of a Tamoxifen Exemestane Adjuvant Multicenter trial substudy.

PURPOSE: Hormonal breast cancer treatment increases menopausal symptoms in women. This study investigated differences between the symptoms associated with either adjuvant tamoxifen or exemestane. PATIENTS AND METHODS: Ten common symptoms were assessed by self-report questionnaire administered to 1,614 consecutive patients at baseline and every 3 months during the first year of a double-blind, randomized trial of postmenopausal women with early hormone receptor-positive breast cancer. Symptoms were categorized as none, mild, moderate, or severe. A hot flash score was calculated at each time point. Symptoms were analyzed by repeated-measures analysis of variance. Each time period was tested repeatedly against the baseline; an overall P value was assigned for each reported symptom. RESULTS: Compliance was excellent, with 7,286 questionnaires analyzed. Baseline symptom prevalence ranged from 2% (vaginal bleeding) to 60% to 70% (bone/muscle aches and low energy). There were no significant differences in vaginal bleeding, mood alteration, or low energy. Patients receiving tamoxifen had significantly more vaginal discharge (P < .0001). Exemestane patients reported more bone/muscle aches (P < .0001), vaginal dryness (P = .0004), and difficulty sleeping (P = .03). In both groups, the hot flash score peaked at 3 months and decreased thereafter. At 12 months, patients receiving tamoxifen had a significantly higher mean hot flash score (P = .03), with daily hot flashes increasing from baseline by 33% compared with a 7% increase from baseline with exemestane. CONCLUSION: At 12 months, exemestane was associated with fewer hot flashes and less vaginal discharge than tamoxifen, but with more vaginal dryness, bone/muscle aches, and difficulty sleeping. Symptoms were common in both groups.