Front line therapy with gemcitabine(G) administered immediately prior to pemetrexed (P) for patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC): Final report of a phase II clinical trial

Abstract

7116 Background: P and G have well demonstrated, single-agent activity in pts with locally advanced or metastatic NSCLC. This phase II study was designed to determine the activity of the combination of PG when G was administered immediately prior to P on day 8 of a 21-day cycle. Methods: Pts with Stage IIIB/IV NSCLC were enrolled. Treatment was G 1250 mg/m2 on D 1 and 8, with P 500 mg/m2 on D 8, immediately following G. Treatment was repeated every 21 days for 6 cycles. Pts received folic acid, vitamin B12 and steroid prophylaxis. Results: 54 pts (32 M/22 F) were enrolled in the study. Median age was 65.0 (range = 43 - 87) years, ECOG PS 0: 1 = 35.2%: 57.4%; Stage IIIB (9.3%), Stage IV (90.7%); Histology: adeno (61.1%) squamous (18.5%), and large cell (5.6%). Median dose intensity was 83.2% for P and 82.2% for G. Grade 3 toxicities were neutropenia (12.0%), thrombocytopenia (8.0%), dyspnea (16.0%), febrile neutropenia (10.0%), anemia (4.0%), fatigue (18.0%), nausea (10.0%), vomiting (8.0%), and rash (2.0%). Grade 4 toxicities were neutropenia (28%), thrombocytopenia (4%), dyspnea (6%), anemia (0%), fatigue (4%), nausea (0%), vomiting (0%), rash (0%). Five patients (10%) experienced Grade 1 alopecia. Median TTPD was 4.4 months and survival was 10.6 months. There were 0 CR, 16 PR (35.6%), 16 SD (35.6%), and 12 PD (26.7%), for an overall best response rate of 35.6%. Conclusions: In this study, PG had a disease control rate (ORR + SD) of 71.1% in the front-line treatment of NSCLC, suggesting that this is an active doublet. Administering P on D 8 rather than D 1 did not seem to negatively impact the therapeutic index. [Table: see text]

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

“…This MTD level is comparable to the dose used for 21-day cycles, in which gemcitabine was administered at 1250 mg/m 2 on days 1 and 8 and pemetrexed was given at 500 mg/m 2 on either day 1 or 8. 14,15,17,18 In the present study, the MTD dose was well tolerated in the phase 2 study, with neutropenia (28.3%) as the most common toxicity. Furthermore, the dose intensity exceeded previous studies employing 21-day cycles of gemcitabine and pemetrexed in locally advanced or metastatic NSCLC (77.3% for gemcitabine and 87.2% for pemetrexed).…”

“…Two previous trials of 21-day gemcitabine and pemetrexed in first-line NSCLC without a 90-minute delay between treatments were conducted by West et al (which administered gemcitabine on days 1 and 8 and pemetrexed on day 8) 18 and Treat et al (which administered gemcitabine on days 1 and 8 and pemetrexed on day 1). 17 In these two trials, the median dose intensities were 82.2% and 76.8% for gemcitabine and 83.2% and 93.9% for pemetrexed.…”

“…12,13 Initial phase 2 studies in NSCLC combining these two agents have employed a 90minute delay between administration. 14,15 A pharmacokinetic study, 16 however, and subsequent phase 2 studies of the combination 17,18 have indicated that this delay in administration may be unnecessary. Most clinical studies employing pemetrexed and gemcitabine in stage IIIB-IV NSCLC have used a 21-day schedule.…”

“…Most clinical studies employing pemetrexed and gemcitabine in stage IIIB-IV NSCLC have used a 21-day schedule. 14,15,17,18 By comparison, dosing once every 2 weeks theoretically offers the potential of increased dose intensity and added patient convenience. The potential benefit of this regimen is supported by the findings of a phase 2 study of docetaxel and gemcitabine, in which a twicemonthly regimen resulted in a response rate of 55.7%.…”