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Randomized phase II study comparing weekly docetaxel-cisplatin vs. gemcitabine-cisplatin in elderly or poor performance status patients with advanced non-small cell lung cancer

Abstract

Background

Docetaxel/cisplatin (DP) and gemcitabine/cisplatin (GP) are standard treatment regimens for advanced non-small cell lung cancer (NSCLC). In spite of potent efficacy, the conventional 1-day DP is regarded as having more toxicity as compared with GP. There is increasing interest in a biweekly split administration of DP to reduce its toxicity. Hypothesis was that first-line biweekly DP is as safe as GP in the elderly or poor performance status (PS) patients.

Methods

Chemotherapy-naïve patients with advanced NSCLC (IIIB/IV) who were elderly (65<) or PS (ECOG 2) were randomized to DP or GP arm by balancing for ECOG (0–1 vs. 2) and stage (IIIB vs. IV). DP comprised docetaxel (35 mg/m2)/cisplatin (30 mg/m2) iv on days 1 and 8, every 3 weeks. GP comprised gemcitabine (1000 mg/m2)/cisplatin (30 mg/m2) iv on days 1 and 8, every 3 weeks. Chemotherapy lasted up to 4–6 cycles or until progression. Primary endpoint was safety (proportion of grade 3/4 toxicities). Planned sample size was 49 patients in each arm.

Results

From November 2009 to August 2012, a total of 99 patients were randomized (DP 50/GP 49) from nine institutions. Adenocarcinoma and squamous cell carcinoma were observed in 62% and 33% of patients, respectively. Toxicity profiles were comparable for both arms and the differences were not statistically significant except for anemia and leucocytopenia. Any grade of anemia (86 vs. 98%) and of leucocytopenia (18 vs. 43%) was more common in the GP arm with statistical significance. Oral mucositis tended to be predominant in the DP arm. Patients in the DP arm (51%) suffered grade 3 or higher toxicities as did 47% in the GP arm (47%). The most common grade 3 or higher toxicities were as follows: In the DP arm, neutropenia (8%), leucopenia (8%), anemia (4%), pneumonia with normal ANC (4%) and febrile neutropenia (2%) were observed. In the GP arm, anemia (15%), neutropenia (15%), pneumonia with normal ANC (4%), thrombocytopenia (4%) and leucopenia (2%) were observed. The best overall response rates (CR + PR) for the DP and GP arms were 20.0 and 21% with no CR, respectively, and disease control rates (CR + PR + SD) were 70.0 and 76%, respectively. Median progression-free survival and median overall survival were 3.7 and 14.9 months in the DP arm and 5.6 and 20.8 months in the GP arm, respectively.

Conclusion

This study showed that DP is similar to GP in terms of efficacy and toxicity in treatment of elderly or poor performance patients. Both regimens showed similar grade 3/4 toxicities with different profiles.

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References

  1. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH, Eastern Cooperative Oncology Group (2002) Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. N Engl J Med 346(2):92–98

    CAS  Article  PubMed  Google Scholar 

  2. Al-Batran SE, Hozaeel W, Tauchert FK, Hofheinz RD, Hinke A, Windemuth-Kieselbach C, Hübner A, Burmester M, Koenigsmann M, Wiegand J, Zur Hausen G, Linsse B, Kuhl R, Pauligk C, Arbeitsgemeinschaft Internistische Onkologie (AIO) (2015) The impact of docetaxel-related toxicities on health-related quality of life in patients with metastatic cancer (QoliTax). Ann Oncol 26(6):1244–1248

    Article  PubMed  Google Scholar 

  3. Niho S, Ohe Y, Kakinuma R, Kubota K, Matsumoto T, Ohmatsu H, Goto K, Nishiwaki Y (2002) Phase II study of docetaxel and cisplatin administered as three consecutive weekly infusions for advanced non-small cell lung cancer. Lung Cancer 35(2):209–214

    Article  PubMed  Google Scholar 

  4. Ohe Y, Niho S, Kakinuma R, Kubota K, Ohmatsu H, Goto K, Nokihara H, Kunitoh H, Saijo N, Aono H, Watanabe K, Tango M, Yokoyama A, Nishiwaki Y (2004) A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients. Ann Oncol 15(1):45–50

    CAS  Article  PubMed  Google Scholar 

  5. Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, Yamamoto N, Yoshioka H, Minato K, Sawa T, Iwamoto Y, Saka H, Shibata T, Nakamura S, Ando M, Nakagawa K, Saijo N, Tamura T (2015) Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol 33(6):575–581

    CAS  Article  PubMed  Google Scholar 

  6. Lee KW, Lim JH, Kim JH, Lee CT, Lee JS (2008) Weekly low-dose docetaxel for salvage chemotherapy in pretreated elderly or poor performance status patients with non-small cell lung cancer. J Korean Med Sci 23(6):992–998

    Article  PubMed  PubMed Central  Google Scholar 

  7. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    CAS  Article  Google Scholar 

  8. Qi WX, Tang LN, He AN, Shen Z, Lin F, Yao Y (2012) Doublet versus single cytotoxic agent as first-line treatment for elderly patients with advanced non-small cell lung cancer: a systematic review and meta-analysis. Lung 190(5):477–485

    CAS  Article  PubMed  Google Scholar 

  9. Davidoff AJ, Tang M, Seal B, Edelman MJ (2010) Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 28(13):2191–2197

    Article  PubMed  Google Scholar 

  10. Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Montanino A, Mancuso G, Russo P, Nacci A, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F (2013) Randomized phase III trial of gemcitabine and cisplatin vs. gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: The CAPPA-2 study. Lung Cancer 81(1):77–83

    Article  PubMed  Google Scholar 

  11. Shim BY, Kim CH, Song SH, Ahn MI, Hong EJ, Kim SW, Kim S, Jo MS, Cho DG, Cho KD, Yoo J, Kim HK (2005) The safety and efficacy of second-line single docetaxel (75 mg/m2) therapy in advanced non-small cell lung cancer patients who were previously treated with platinum-based chemotherapy. Cancer Res Treat 37(6):339–343

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M (2006) Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non–small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 24(22):3657–3663

    CAS  Article  PubMed  Google Scholar 

  13. Park SH, Choi SJ, Kyung SY, An CH, Lee SP, Park JW, Jeong SH, Cho EK, Shin DB, Hoon Lee J (2007) Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first-line therapy in advanced nonsmall cell lung cancer. Cancer 109(4):732–740

    CAS  Article  PubMed  Google Scholar 

  14. Camps C, Massuti B, Jiménez A, Maestu I, Gómez RG, Isla D, González JL, Almenar D, Blasco A, Rosell R, Carrato A, Viñolas N, Batista N, Girón CG, Galán A, López M, Blanco R, Provencio M, Diz P, Felip E, Spanish Lung Cancer Group (2006) Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group. Ann Oncol 17:467–472

    CAS  Article  PubMed  Google Scholar 

  15. Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP (2003) Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non–small-cell lung cancer: the TAX 326 study group. J Clin Oncol 21:3016–3024

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Hoon-Kyo Kim.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study.

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Jang, J., Kim, HK., Cho, B.C. et al. Randomized phase II study comparing weekly docetaxel-cisplatin vs. gemcitabine-cisplatin in elderly or poor performance status patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol 79, 873–880 (2017). https://doi.org/10.1007/s00280-017-3289-6

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  • DOI: https://doi.org/10.1007/s00280-017-3289-6

Keywords

  • Non-small cell lung cancer
  • Docetaxel
  • Gemcitabine
  • Cisplatin
  • Elderly patients