Drugs & Aging

, Volume 32, Issue 6, pp 487–493 | Cite as

Phase II Study of a Platinum-Based Adapted Chemotherapy Regimen Combined with Radiotherapy in Patients 75 Years and Older with Esophageal Cancer

  • Stéphanie Servagi-Vernat
  • Gilles Créhange
  • Bernard Roullet
  • Valentine Guimas
  • Philippe Maingon
  • Marc Puyraveau
  • Jean François Bosset
Original Research Article

Abstract

Background and objective

The management of elderly patients with cancer is a therapeutic challenge and a public health problem. The aim of this phase II single-arm study was to evaluate the acute toxicities and efficacy of chemoradiotherapy (CRT) comprising a single platinum-based agent combined with radiotherapy in elderly patients with esophageal cancer.

Methods

Between March 2000 and October 2011, patients aged 75 years and older were prospectively treated with external beam radiotherapy combined with cisplatin or oxaliplatin. Other selection criteria included Eastern Cooperative Oncology Group status 0–2, disease stage II–III, squamous cell carcinoma or adenocarcinoma, and an adequate biological profile. The radiotherapy dose was 50 Gy administered over 5 weeks to the primary tumor and involved lymph nodes. Cisplatin was planned at a dose of 75 mg/m2 on days 1 and 21 and oxaliplatin at 85 mg/m2 on days 1, 15, and 29. Treatment was delivered an outpatient setting.

Results

Thirty patients with a mean age of 85.2 (range 79.4–92.0) years were included; 28 completed the treatment. Dysphagia was the only grade 4 toxicity to occur during the study; no grade 5 toxicities were observed. Six weeks after the completion of treatment, 16 patients (53.3 %) were in complete response. Two patients in complete response died from pneumonitis 5 and 7 months after CRT. With a 36-month median follow-up, 18 patients died from cancer (nine from local failure, nine from metastasis). Seven patients died from other causes and two patients were alive 40.3 and 56 months after the end of their treatment. Three-year overall survival was 22.2 %.

Conclusions

Selected elderly patients with esophageal cancer and adequate functional status should not be excluded from CRT and may be able to tolerate the treatment with acceptable acute toxicities. However, mid-term efficacy is mediocre. Our data also suggest that the therapeutic ratio or locoregional control might be improved by increasing the radiotherapy dose or by testing new radiosensitizer agents since half of the failures were within the treated volume.

Trial Registration: EudraCT no. 2009-010113-76.

Notes

Acknowledgments

This study was funded in part by La Ligue Contre le Cancer. We would like to thank Philip Bastable for help with translation and proof-reading.

Conflict of interest

SSV, GC, BR, VG, PM, MP and JFB declare that they have no competing interests.

Authors’ contributions

SSV and GC drafted the manuscript. SSV, GC, JFB, PM, BR and VG contributed to the design of the study and included patients in their center. MP performed the statistical analysis. All authors read and approved the final manuscript.

References

  1. 1.
    Chino O, Makuuchi H, Machimura T, Mizutani K, Shimada H, Kanno K, et al. Treatment of esophageal cancer in patients over 80 years old. Surg Today. 1997;27(1):9–16.PubMedCrossRefGoogle Scholar
  2. 2.
    Mohansingh MP. Mortality of oesophagal surgery in the elderly. Br J Surg. 1976;63(8):579–80.PubMedCrossRefGoogle Scholar
  3. 3.
    Peracchia A, Bardini R, Ruol A. Carcinoma of the oesophagus in the elderly (70 years of age or over). Indications and results of surgery. Dis Esophagus. 1988;1:147–52.Google Scholar
  4. 4.
    Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Servagi-Vernat S, Bosset M, Crehange G, Buffet-Miny J, Puyraveau M, Maingon P, et al. Feasibility of chemoradiotherapy for oesophageal cancer in elderly patients aged > or = 75 years: a prospective, single-arm phase II study. Drugs Aging. 2009;26(3):255–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRefGoogle Scholar
  7. 7.
    ICRU. Prescribing recording and reporting photon beam therapy (supplement to ICRU Report 50), ICRU Report 62. Bethesda: ICRU; 1999.Google Scholar
  8. 8.
    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(3):205–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Ogilvie AL, Dronfield MW, Ferguson R, Atkinson M. Palliative intubation of oesophagogastric neoplasms at fibreoptic endoscopy. Gut. 1982;23(12):1060–7.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Cancer therapy evaluation program common terminology criteria for adverse events Version 3.0; DCTD, NCI, NIH, DHHS; 2003. http://ctep.cancer.gov.
  11. 11.
    Panettiere FJ, Leichman L, O’Bryan R, Haas C, Fletcher W. Cis-diamminedichloride platinum(II), an effective agent in the treatment of epidermoid carcinoma of the esophagus. A preliminary report of an ongoing Southwest Oncology Group study. Cancer Clin Trials. 1981;4(1):29–31.PubMedGoogle Scholar
  12. 12.
    Steiger Z, Franklin R, Wilson RF, Leichman L, Asfaw I, Vaishanpayan G, et al. Complete eradication of squamous cell carcinoma of the esophagus with combined chemotherapy and radiotherapy. Am Surg. 1981;47(3):95–8.PubMedGoogle Scholar
  13. 13.
    Sternberg C, Kelsen D, Dukeman M, Leichman L, Heelan R. Carboplatin: a new platinum analog in the treatment of epidermoid carcinoma of the esophagus. Cancer Treat Rep. 1985;69(11):1305–7.PubMedGoogle Scholar
  14. 14.
    Petrelli F, Coinu A, Riboldi V, Borgonovo K, Ghilardi M, Cabiddu M, et al. Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: a systematic review and meta-analysis of published studies. Oral Oncol. 2014;50(11):1041–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Micheletti E, La Face B, Bianchi E, Cagna E, Sartori E. Locally advanced carcinoma of the cervix uteri (stage IIB-IIIB TNM-UICC): radiotherapy combined with simultaneous daily low-dose platinum. Phase II study (in Italian). Radiol Med. 1996;91(5):628–34.PubMedGoogle Scholar
  16. 16.
    Azria D, Riou O, Rebillard X, Thezenas S, Thuret R, Fenoglietto P, et al. Combined chemoradiation therapy with twice-weekly gemcitabine and cisplatin for organ preservation in muscle-invasive bladder cancer: long-term results of a phase 1 trial. Int J Radiat Oncol Biol Phys. 2014;88(4):853–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Ajani JA, Walsh G, Komaki R, Morris J, Swisher SG, Putnam JB Jr, et al. Preoperative induction of CPT-11 and cisplatin chemotherapy followed by chemoradiotherapy in patients with locoregional carcinoma of the esophagus or gastroesophageal junction. Cancer. 2004;100(11):2347–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Anderson SE, Minsky BD, Bains M, Hummer A, Kelsen D, Ilson DH. Combined modality chemoradiation in elderly oesophageal cancer patients. Br J Cancer. 2007;96(12):1823–7.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Mak RH, Mamon HJ, Ryan DP, Miyamoto DT, Ancukiewicz M, Kobayashi WK, et al. Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older. Dis Esophagus. 2010;23(4):316–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Haj Mohammad N, Hulshof MC, Bergman JJ, Geijsen D, Wilmink JW, van Berge Henegouwen MI, et al. Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma. BMC Cancer. 2014;14:56.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20(5):1167–74.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Stéphanie Servagi-Vernat
    • 1
  • Gilles Créhange
    • 2
  • Bernard Roullet
    • 4
  • Valentine Guimas
    • 1
  • Philippe Maingon
    • 2
  • Marc Puyraveau
    • 3
  • Jean François Bosset
    • 1
  1. 1.Department of Radiation OncologyBesançon University HospitalBesançonFrance
  2. 2.Department of Radiation OncologyCancer center DijonDijonFrance
  3. 3.Clinical Methodology CenterBesançon University HospitalBesançonFrance
  4. 4.Department of Radiation OncologyPoitiers University HospitalPoitiersFrance

Personalised recommendations