Multicenter Analysis of mFOLFOX6 with Oxaliplatin Stop-and-Go Strategy Using Oral Uracil-Tegafur with Leucovorin for Unresectable Colorectal Cancer in Elderly Patients

Tetsu Yamamoto, Kuniyuki Katano, Shinichi Sugimoto, Akiyoshi Kanazawa, Eiji Hira, Hiroshi Takeda, Yoshitoshi Sato, Yutaka Yamashiro, Yoshitsugu Tajima, Masahide Ikeguchi

Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Izumo, Japan.
Department of Gastroenterological Surgery, Matsue Red Cross Hospital, Matsue, Japan.
Department of Gastroenterological Surgery, Osaka Red Cross Hospital, Osaka, Japan.
Department of Gastroenterological Surgery, Tottori Red Cross Hospital, Tottori, Japan.
Department of Surgery, Saihaku Hospital, Saihaku, Japan.
Department of Surgery, Shimane Prefectural Central Hospital, Izumo, Japan.
Division of Surgical Oncology, Faculty of Medicine, Tottori University, Yonago, Japan.

DOI: 10.4236/jct.2014.52018                

Abstract

Background: This study evaluated the tolerability and efficacy of intermittent oxaliplatin treatment based on mFOLFOX6 using oral uracil-tegafur(UFT) and leucovorin(LV) maintenance therapy in the treatment of elderly patients with advanced colorectal cancer. Methods: Ten non-elderly patients (<70 years) and 8 elderly patients (>70 years) with advanced/recurrent colorectal cancer were enrolled in this prospective, multicenter cooperative group clinical trial. The mFOLFOX6 regimen was administered for eight cycles with maintenance therapy with oral UFT/LV treatment until progression. In cases with disease progression, mFOLFOX6 was reintroduced. Results: Grade 2 peripheral neuropathy was noted in 30.0% and 25.0% of the elderly and non-elderly patients, respectively. The observed time to treatment failure (TTF) was 6.3 months in the elderly patients and 6.4 months in the non-elderly patients. The disease control rate was 83.3% in each group. Conclusion: Our new stop-and-go strategy using oral UFT/LV is well-tolerated and effective even in elderly patients.

Keywords

Colorectal Cancer; Oxaliplatin; Uracil-Tegafur (UFT); Leucovorin; Elderly Patient; Stop-and-Go

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	I. Hyodo, et al., “Present Status and Perspectives of Colorectal Cancer in Asia: Colorectal Cancer Working Group report in 30th Asia-Pacific Cancer Conference,” Japanese Journal of Clinical Oncology, Vol. 40, Suppl. 1, 2010, pp. I38-I43. http://dx.doi.org/10.1093/jjco/hyq125
[2]	R. M. Goldberg, et al., “A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients with Previously Untreated Metastatic Colorectal Cancer,” Journal of Clinical Oncology, Vol. 22, No. 1, 2004, pp. 23-30. http://dx.doi.org/10.1200/JCO.2004.09.046
[3]	S. Sugimoto, et al., “Multicenter Safety Study of mFOLFOX6 for Unresectable Advanced/Recurrent Colorectal Cancer in Elderly Patients,” Journal of Experimental & Clinical Cancer Research, Vol. 28, 2009, p. 109. http://dx.doi.org/10.1186/1756-9966-28-109
[4]	C. Tournigand, et al., “OPTIMOX1: A Randomized Study of FOLFOX4 or FOLFOX7 with Oxaliplatin in a Stop-and-Go Fashion in Advanced Colorectal Cancer—A GERCOR Study,” Journal of Clinical Oncology, Vol. 24, No. 3, 2006, pp. 394-400. http://dx.doi.org/10.1200/JCO.2005.03.0106
[5]	J. F. Bosset, et al., “Preoperative Radiochemotherapy in Rectal Cancer: Long-Term Results of a Phase II Trial,” International Journal of Radiation Oncology *Biology* Physics, Vol. 46, No. 2, 2000, pp. 323-327. http://dx.doi.org/10.1016/S0360-3016(99)00411-3
[6]	M. M. Borner, et al., “Patient Preference and Pharmacokinetics of Oral Modulated UFT versus Intravenous Fluorouracil and Leucovorin: A Randomised Crossover Trial in Advanced Colorectal Cancer,” European Journal of Cancer, Vol. 38, No. 3, 2002, pp. 349-358. http://dx.doi.org/10. 1016/S0959-8049(01)00371-9
[7]	M. o. H. LaW, “Ethical Guidelines for Clinical Studies,” http://www.med.or.jp/wma/helsinki08_j.html
[8]	E. P. f. M. R. I. H. S., “18th WMA General Assembly. World Medical Association Declaration of Helsinki,” 2008. http://www.med.or.jp/wma/helsinki08_j.html
[9]	I. NC, Common Terminology Criteria for Adverse Events v3.0, 2006.
[10]	P. Therasse, 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,” Journal of the National Cancer Institute, Vol. 92, No. 3, 2000, pp. 205-216. http://dx.doi.org/10.1093/jnci/92.3.205
[11]	F. Maindrault-Goebel, et al., “Oxaliplatin Added to the Simplified Bimonthly Leucovorin and 5-Fluorouracil Regimen as Second-Line Therapy for Metastatic Colorectal Cancer (FOLFOX6). GERCOR,” European Journal of Cancer, Vol. 35, No. 9, 1999, pp. 1338-1342. http://dx.doi.org/10.1016/S0959-8049(99)00149-5
[12]	T. Shimizu, et al., “Oxaliplatin/Fluorouracil/Leucovorin (FOLFOX4 and Modified FOLFOX6) in Patients with Refractory or Advanced Colorectal Cancer: Post-Approval Japanese Population Experience,” International Journal of Clinical Oncology, Vol. 12, No. 3, 2007, pp. 218-223. http://dx.doi.org/10. 1007/s10147-007-0658-x
[13]	L. Gamelin, et al., “Prevention of Oxaliplatin-Related Neurotoxicity by Calcium and Magnesium Infusions: A Retrospective Study of 161 Patients Receiving Oxaliplatin Combined with 5-Fluorouracil and Leucovorin for Advanced Colorectal Cancer,” Clinical Cancer Research, Vol. 10, No. 12 Pt 1, 2004, pp. 4055-4061.
[14]	F. Eckel, et al., “Prevention of Oxaliplatin-Induced Neuropathy by Carbamazepine. A Pilot Study,” Dtsch Med Wochenschr, Vol. 127, No. 3, 2002, pp. 78-82. http://dx.doi.org/10.1055/s-2002-19594
[15]	S. Cascinu, et al., “Neuroprotective Effect of Reduced Glutathione on Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial,” Journal of Clinical Oncology, Vol. 20, No. 16, 2002, pp. 3478-3483. http://dx.doi.org/10. 1200/JCO.2002.07.061
[16]	M. Penz, et al., “Subcutaneous Administration of Amifostine: A Promising Therapeutic Option in Patients with Oxaliplatin-Related Peripheral Sensitive Neuropathy,” Annals of Oncology, Vol. 12, No. 3, 2001, pp. 421-422. http://dx.doi.org/10.1023/A:1011184609963
[17]	C. Gedlicka, et al., “Effective Treatment of Oxaliplatin-Induced Cumulative Polyneuropathy with Alpha-Lipoic Acid,” Journal of Clinical Oncology, Vol. 20, No. 15, 2002, pp. 3359-3361. http://dx.doi.org/10.1200/JCO.2002.99.502
[18]	A. Grothey, “Oxaliplatin-Safety Profile: Neurotoxicity,” Semin Oncol, Vol. 30, No. 4, Suppl. 15, 2003, pp. 5-13. http://dx.doi.org/10.1016/S0093-7754(03)00399-3
[19]	S. C. Montamat, B. J. Cusack and R. E. Vestal, “Management of Drug Therapy in the Elderly,” The New England Journal of Medicine, Vol. 321, No. 5, 1989, pp. 303-309. http://dx.doi.org/10.1056/NEJM 198908033210507
[20]	D. J. Greenblatt, E. M. Sellers and R. I. Shader, “Drug Therapy: Drug Disposition in Old Age,” The New England Journal of Medicine, Vol. 306, No. 18, 1982, pp. 1081-1088. http://dx.doi.org/10.1056/ NEJM198205063061804
[21]	R. M. Goldberg, et al., “Pooled Analysis of Safety and Efficacy of Oxaliplatin plus Fluorouracil/Leucovorin Administered Bimonthly in Elderly Patients with Colorectal Cancer,” Journal of Clinical Oncology, Vol. 24, No. 25, 2006, pp. 4085-4091. http://dx.doi.org/10.1200/JCO.2006.06.9039
[22]	A. Grothey, et al., “Survival of Patients with Advanced Colorectal Cancer Improves with the Availability of Fluorouracil-Leucovorin, Irin Otecan, and Oxaliplatin in the Course of Treatment,” Journal of Clinical Oncology, Vol. 22, No. 7, 2004, pp. 1209-1214. http://dx.doi.org/10.1200/JCO. 2004.11.037