A comparison of toxicity profile of gemcitabine monotherapy versus etoposide/cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer

Ved Prakash, Arpita Singh, Surya Kant, Ajay K. Verma, Prachi Saxena, Ankit Bhatia


Background: Lung cancer is the leading cause of cancer deaths globally in which about 40% patients reporting in advanced stage disease. Both platinum and non platinumcombinations have been shown to be equally efficacious as initial first-line treatment of advanced non-small cell lung cancer (NSCLC), however because of the toxicity of cisplatin, combination treatment can only be administered to a minority of patients in good general health. Gemcitabine could be combined with one of the other new agents to create novel non-platinum-doublet combinations with efficacy and/or toxicity profile superior to that of standard platinum based combinations. Hence, this study was conducted to compare the toxicity profiles of gemcitabine monotherapy and the cisplatin/etoposide combination therapy.

Methods: This was a randomized prospective study, which included 96 patients selected on the basis of histologically or cytologically confirmed Stage III B or IV of NSCLC. Study was divided into two arms-Arm A received gemcitabine monotherapy in a dose of 1000 mg/m2 on day 1 and 5 of the cycle andrepeated after every 3 weeks while Arm B received cisplatin (25 mg/m2 on day 1, 2 and 3) + etoposide (100 mg/m2). Patient were evaluated for adverse events by following World Health Organization grading of toxicity.

Results: Out of the 96 patients enrolled in the study, 74 (77.0%) patients were eligible and were analyzed. Of these, 36 (37.5%) patients belonged to Arm A and 38 (39.5%) to Arm B. Transient vomiting (45.8% vs. 37.5%), leukopenia (33.3% vs. 8.3%) were seen more in Arm A, while thrombocytopenia (33.3% vs. 12.5%), patchy hair loss (68.4% vs. 16.6%) was seen more in Arm B. Nephrotoxicity was seen almost similarly in both the groups.

Conclusions: Single-agent gemcitabine appears to have a safer toxicity profile than the combination cisplatin-etoposide in the first-line chemotherapy of advanced NSCLC. With less toxic anticancer drugs like gemcitabine, the physician now has greater choice in choosing treatment, which can have better effect on the patients concerned.


Non-small cell lung cancer, Chemotherapy, Toxicity

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Harris RE, Zang EA, Anderson JI, Wynder EL. Race and sex differences in lung cancer risk associated with cigarette smoking. Int J Epidemiol. 1993;22(4):592-9.

Wynder EL, Hoffmann D. Smoking and lung cancer: Scientific challenges and opportunities. Cancer Res. 1994;54(20):5284-95.

Word Health Organization. Tobacco or Health: A Global Status Report. Geneva: World Health Organization; 1997.

Kumar R, Prakash S, Kushwah AS, Vijayan VK. Breath carbon monoxide concentration in cigarette and bidi smokers in India. Indian J Chest Dis Allied Sci. 2010;52(1):19-24.

Ramalingam S, Belani C. Systemic chemotherapy for advanced non-small cell lung cancer: Recent advances and future directions. Oncologist. 2008;13 Suppl 1:5-13.

Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ. 1995;311(7010):899-909.

Manegold C, Bergman B, Chemaissani A, Dornoff W, Drings P, Kellokumpu-Lehtinen P, et al. Single-agent gemcitabine versus cisplatin-etoposide: Early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer. Ann Oncol. 1997;8(6):525-9.

Ardizzoru A, Martin C. Gemcitabine toxicity profile and efficacy unaffected by age in advanced non-small-cell lung cancer (NSCLC). Ann Oncol. 1994;5 Suppl 8:60.

Perng RP, Chen YM, Ming-Liu J, Tsai CM, Lin WC, Yang KY, et al. Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study. J Clin Oncol. 1997;15(5):2097-102.

Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, et al. Clinical-benefit response in advanced non-small-cell lung cancer: A multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001;12(9):1221-30.

Franklin HR, Simonetti GP, Dubbelman AC, ten Bokkel Huinink WW, Taal BG, Wigbout G, et al. Toxicity grading systems. A comparison between the WHO scoring system and the Common Toxicity Criteria when used for nausea and vomiting. Ann Oncol. 1994;5(2):113-7.

Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: The Southwest oncology group experience. J Clin Oncol. 1991;9(9):1618-26.

Ramalingam S, Belani CP. State-of-the-art chemotherapy for advanced non-small cell lung cancer. Semin Oncol. 2004;31 1 Suppl 1:68-74.

Zwitter M, Kovac V, Smrdel U, Vrankar M, Zadnik V. Gemcitabine in brief versus prolonged low-dose infusion, both combined with cisplatin, for advanced non-small cell lung cancer: A randomized phase II clinical trial. J Thorac Oncol. 2009;4(9):1148-55.

Zwitter M, Kovac V, Rajer M, Vrankar M, Smrdel U. Two schedules of chemotherapy for patients with non-small cell lung cancer in poor performance status: A phase II randomized trial. Anticancer Drugs. 2010;21(6):662-8.

Rodriguez J, Cortes J, Calvo E, Azinovic I, Fernandez-Hildago O, Martinez-Monge R, et al. Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma. Cancer. 2000;89(12):2622-9.

Ceribelli A, Gridelli C, De Marinis F, Fabi A, Gamucci T, Cortesi E, et al. Prolonged gemcitabine infusion in advanced non-small cell lung carcinoma: A randomized phase II study of two different schedules in combination with cisplatin. Cancer. 2003;98(2):337-43.

Novello S, Bruzzi P, Barone C. Phase III study in stage IV non-small-cell lung cancer (NSCLC) patients (pts) treated with two cycles of cisplatin/gemcitabine followed by a randomization to three additional cycles of the same combination or gemcitabine alone. Proc Am Soc Clin Oncol. 2005;23:633S (Abstr 7051).

Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999;17(1):12-8.