Randomized, double-blind, placebo-controlled phase II study of single-agent oral talactoferrin in patients with locally advanced or metastatic non-small-cell lung cancer that progressed after chemotherapy.

PURPOSE: To investigate the activity and safety of oral talactoferrin (TLF) in patients with stages IIIB to IV non-small-cell lung cancer (NSCLC) for whom one or two prior lines of systemic anticancer therapy had failed. PATIENTS AND METHODS: Patients (n = 100) were randomly assigned to receive either oral TLF (1.5 g in 15 mL phosphate-based buffer) or placebo (15 mL phosphate-based buffer) twice per day in addition to supportive care. Oral TLF or placebo was administered for a maximum of three 14-week cycles with dosing for 12 consecutive weeks followed by 2 weeks off. The primary objective was overall survival (OS) in the intent-to-treat (ITT) patient population. Secondary objectives included progression-free survival (PFS), disease control rate (DCR), and safety. RESULTS: TLF was associated with improvement in OS in the ITT patient population, meeting the protocol-specified level of significance of a one-tailed P = .05. Compared with the placebo group, median OS increased by 65% in the TLF group (3.7 to 6.1 months; hazard ratio, 0.68; 90% CI, 0.47 to 0.98; P = .04 with one-tailed log-rank test). Supportive trends were also observed for PFS and DCR. TLF was well tolerated and, generally, there were fewer adverse events (AEs) and grade ≥ 3 AEs reported in the TLF arm. AEs were consistent with those expected in late-stage NSCLC. CONCLUSION: TLF demonstrated an apparent improvement in OS in patients with stages IIIB to IV NSCLC for whom one or two prior lines of systemic anticancer therapy had failed and was well tolerated. These results should be confirmed in a global phase III trial.

Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment.

PURPOSE: The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. PATIENTS AND METHODS: Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. RESULTS: A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. CONCLUSION: This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.

Chemotherapy in biliary tract carcinomas: results in India.

Epidemiology data from India suggest that biliary tract carcinomas occur primarily in the older population. Because of the absence of early symptoms, most patients present with advanced disease, and the outcome has been disappointing even in patients with resectable tumors who have undergone aggressive surgery. Although there is no standard therapy, data from recent clinical trials warrant further investigation of the role of chemotherapy in biliary tract carcinoma. In view of the favorable toxicity profile and observed efficacy of gemcitabine in advanced biliary tract cancers, its evaluation in combination with other active, potentially synergistic cytotoxic drugs such as cisplatin, capecitabine, and carboplatin should be studied with an aim to improve therapeutic efficacy and survival.