Cancer Res Treat.  2016 Apr;48(2):465-472. 10.4143/crt.2015.061.

A Phase II Study of Weekly Paclitaxel Plus Gemcitabine as a Second-Line Therapy in Patients with Metastatic or Recurrent Small Cell Lung Cancer

• Yun T
• Kim HT
• Han JY
• Yoon SJ
• Kim HY
• Nam BH
• Lee JS

• KMID: 2454322
• DOI: http://doi.org/10.4143/crt.2015.061

Abstract

PURPOSE
Paclitaxel (P) and gemcitabine (G) are clinically synergistic in small cell lung cancer (SCLC). We evaluated the efficacy of PG as a salvage treatment for SCLC patients whose disease progressed after a platinum-containing regimen.
MATERIALS AND METHODS
Eligibility included histologically confirmed SCLC, one dimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and progressive disease after platinum-based chemotherapy. Treatment consisted of P (80 mg/m2) and G (1,000 mg/m2) on days 1 and 8 of each cycle of 21 days until disease progression.
RESULTS
Thirty-three patients seen between December 2005 and February 2009 were selected into this study. Thirty patients (91%) had received irinotecan-platinum, and three had received etoposide-platinum. Sixteen patients (49%) had a treatment-free interval of less than 3 months. The overall response rate was 30.3% (29.4% in sensitive relapse and 31.3% in refractory relapse). The median time to progression was 12.0 weeks and median overall survival (OS) 31.0 weeks, with a 1-year OS rate of 30.3%. Toxicities were moderate and manageable with 18.2% grade (G) 4 neutropenia, 24.2% G3 thrombocytopenia, 6.1% G3 sensory neuropathy, and 3% G3 asthenia. One patient developed febrile neutropenia.
CONCLUSION
Second-line paclitaxel and gemcitabine were well-tolerated and moderately active in SCLC patients previously treated with platinum-based chemotherapy.

Keyword

Second-line; Paclitaxel; Gemcitabine; Small cell lung carcinoma

MeSH Terms

Asthenia
Disease Progression
Drug Therapy
Febrile Neutropenia
Humans
Neutropenia
Paclitaxel*
Recurrence
Salvage Therapy
Small Cell Lung Carcinoma*
Thrombocytopenia
Paclitaxel

Figure

• 

  Fig. 1. Progression-free survival (PFS) and overall survival (OS).

Reference

References

1. Perez-Soler R, Glisson BS, Lee JS, Fossella FV, Murphy WK, Shin DM, et al. Treatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan. J Clin Oncol. 1996; 14:2785–90.

2. Furuse K, Kubota K, Kawahara M, Takada M, Kimura I, Fujii M, et al. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Japan Lung Cancer Vinorelbine Study Group. Oncology. 1996; 53:169–72.

3. Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998; 77:347–51.

4. van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlosser NJ, Postmus PE, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001; 12:557–61.

5. Eckardt JR. Topotecan in relapsed small-cell lung cancer: can good things come in small packages? Clin Lung Cancer. 2003; 4:229–30.

6. Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol. 1997; 15:2090–6.

7. Ardizzoni A, Manegold C, Debruyne C, Gaafar R, Buchholz E, Smit EF, et al. European Organization for Research and Treatment of Cancer (EORTC) 08957 phase II study of topotecan in combination with cisplatin as second-line treatment of refractory and sensitive small cell lung cancer. Clin Cancer Res. 2003; 9:143–50.

8. Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006; 26:777–81.

9. Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, et al. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003; 21:1550–5.

10. Edelman MJ, Quam H, Mullins B. Interactions of gemcitabine, carboplatin and paclitaxel in molecularly defined non-small-cell lung cancer cell lines. Cancer Chemother Pharmacol. 2001; 48:141–4.

11. Shord SS, Faucette SR, Gillenwater HH, Pescatore SL, Hawke RL, Socinski MA, et al. Gemcitabine pharmacokinetics and interaction with paclitaxel in patients with advanced non-small-cell lung cancer. Cancer Chemother Pharmacol. 2003; 51:328–36.

12. Hirsh V, Whittom R, Ofiara L, Desjardins P, Ayoub J, Charpentier D, et al. Weekly paclitaxel and gemcitabine chemotherapy for metastatic non-small cell lung carcinoma (NSCLC): a dose-optimizing phase II trial. Cancer. 2003; 97:2242–7.

13. Recchia F, Saggio G, Cesta G, Candeloro G, Rea S. Paclitaxel plus gemcitabine in advanced non-small cell lung cancer patients with low performance status. Anticancer Res. 2005; 25:409–14.

14. Gillenwater HH, Stinchcombe TE, Qaqish BF, Tyann M, Hensing TA, Socinski MA. A phase II trial of weekly paclitaxel and gemctiabine infused at a constant rate in patients with advanced non-small cell lung cancer. Lung Cancer. 2005; 47:413–9.

15. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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. 2000; 92:205–16.

16. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989; 10:1–10.

17. O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cucevia B, Juhasz G, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006; 24:5441–7.

18. Nair BS, Bhanderi V, Jafri SH. Current and emerging pharmacotherapies for the treatment of relapsed small cell lung cancer. Clin Med Insights Oncol. 2011; 5:223–34.

19. Dongiovanni V, Buffoni L, Berruti A, Dongiovanni D, Grillo R, Barone C, et al. Second-line chemotherapy with weekly paclitaxel and gemcitabine in patients with small-cell lung cancer pretreated with platinum and etoposide: a single institution phase II trial. Cancer Chemother Pharmacol. 2006; 58:203–9.

20. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002; 346:85–91.

21. von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014; 32:4012–9.

22. Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007; 25:2086–92.