Annals of Oncology Advance Access published online on January 15, 2009
Annals of Oncology, doi:10.1093/annonc/mdn715
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Gemcitabine and pemetrexed administered in rapid sequence as front-line chemotherapy for advanced non-small-cell lung cancer: a phase II clinical trial
1 Thoracic Oncology Program, Department of Medical Oncology, Swedish Cancer Institute, Seattle
2 Department of Medicine, Division of Oncology, Stanford Cancer Center, Stanford
3 Department of Internal Medicine, Division of Hematology/Medical Oncology, Ellis Fischel Cancer Center, Columbia
4 Kansas City Cancer Centers, Kansas City
5 United States Statistics, Eli lilly and Company, Indianapolis, IN, USA
6 United States Oncology, Eli Lilly and Company, Indianapolis, USA
* Correspondence to: Dr H. West, Thoracic Oncology Program, Department of Medical Oncology, Swedish Cancer Institute, 1221 Madison Street, Suite 1020, Seattle, WA 98104, USA. Tel: +1-206-386-2424; Fax: +1-206-860-6734; E-mail: howard.west{at}swedish.org
Background: Previous studies of the gemcitabine–pemetrexed combination in patients with late-stage non-small-cell lung cancer (NSCLC) utilized a 90-min delay between gemcitabine and pemetrexed administration. This phase II study evaluated activity when these agents were administered in rapid succession.
Materials and methods: Chemonaive patients with late-stage NSCLC received gemcitabine 1250 mg/m2 on days 1 and 8, with pemetrexed 500 mg/m2 immediately following day 8 gemcitabine every 21 days for six cycles, folic acid, B12, and steroid prophylaxis.
Results: Fifty-four enrolled patients (53 treated) completed a median of four cycles. Median dose intensity was 84% (gemcitabine) and 83% (pemetrexed); 68% of patients required dose adjustments. Response was as follows: complete response, 0; partial response, 7 (13%); stable disease, 29 (54%); progressive disease, 9 (17%); and unknown/unavailable, 9 (17%). Median progression-free and overall survival was 4.6 and 12.4 months, respectively. Common grade 3 or 4 toxic effects were as follows: neutropenia (40%); fatigue and dyspnea (21% each); pneumonia (17%); febrile neutropenia and thrombocytopenia (11% each); and anemia (6%).
Conclusions: The gemcitabine–pemetrexed combination is minimally active in late-stage NSCLC, with a high incidence of grade 3 or 4 toxic effects requiring frequent dose adjustments. A gemcitabine dose <1250 mg/m2 warrants consideration for future trials exploring this doublet. Administering day 8 pemetrexed immediately after gemcitabine does not appear to negatively impact therapeutic index.
gemcitabine, immediate administration, NSCLC, pemetrexed, rapid-sequence administration
Received for publication April 23, 2008. Revision received September 29, 2008. Accepted for publication October 8, 2008.
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  T. M. De Pas, F. Toffalorio, C. Catania, C. Noberasco, G. Spitaleri, L. Spaggiari, and F. De Braud Gemcitabine and pemetrexed combination: the key role of the sequence of drugs administration Ann. Onc., October 1, 2009; 20(10): 1747 - 1748. [Full Text] [PDF]
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