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BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Prospective study of daily low-dose nedaplatin and continuous 5-fluorouracil infusion combined with radiation for the treatment of esophageal squamous cell carcinoma

Authors: Satoshi Osawa, Takahisa Furuta, Ken Sugimoto, Takashi Kosugi, Tomohiro Terai, Mihoko Yamade, Yasuhiro Takayanagi, Masafumi Nishino, Yasushi Hamaya, Chise Kodaira, Takanori Yamada, Moriya Iwaizumi, Kosuke Takagaki, Ken-ichi Yoshida, Shigeru Kanaoka, Mutsuhiro Ikuma

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

Protracted low-dose concurrent chemotherapy combined with radiation has been proposed for enhanced treatment results for esophageal cancer. We evaluated the efficacy and the toxicity of a novel regimen of daily low-dose nedaplatin (cis-diammine-glycolatoplatinum) and continuous infusion of 5-fluorouracil (5-FU) with radiation in patients with esophageal squamous cell carcinoma.

Methods

Between January 2003 and June 2008, 33 patients with clinical stage I to IVB esophageal squamous cell carcinoma were enrolled. Nedaplatin (10 mg/body/day) was administered daily and 5-FU (500 mg/body/day) was administered continuously for 20 days. Fractionated radiotherapy for a total dose of 50.4-66 Gy was administered together with chemotherapy. Additional chemotherapy with nedaplatin and 5-FU was optionally performed for a maximum of 5 courses after chemoradiotherapy. The primary end-point of this study was to evaluate the tumor response, and the secondary end-points were to evaluate the toxicity and the overall survival.

Results

Twenty-two patients (72.7%) completed the regimen of chemoradiotherapy. Twenty patients (60.6%) achieved a complete response, 10 patients (30.3%) a partial response. One patient (3.0%) had a stable disease, and 2 (6.1%) a progressive disease. The overall response rate was 90.9% (95% confidence interval: 75.7%-98.1%). For grade 3-4 toxicity, leukopenia was observed in 75.8% of the cases, thrombocytopenia in 24.2%, anemia in 9.1%, and esophagitis in 36.4%, while late grade 3-4 cardiac toxicity occurred in 6.1%. Additional chemotherapy was performed for 26 patients (78.8%) and the median number of courses was 3 (range, 1-5). The 1-, 2- and 3-year survival rates were 83.9%, 76.0% and 58.8%, respectively. The 1- and 2-year survival rates were 94.7% and 88.4% in patients with T1-3 M0 disease, and 66.2% and 55.2% in patients with T4/M1 disease.

Conclusion

The treatment used in our study may yield a high complete response rate and better survival for each stage of esophageal squamous cell carcinoma.

Trial registration

ClinicalTrials.gov Identifier: NCT00197444
Appendix
Available only for authorised users
Literature
1.
Al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, Cooper J, Byhardt R, Davis L, Emami B: Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol. 1997, 15 (1): 277-284.PubMed
2.
Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B: Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992, 326 (24): 1593-1598.CrossRefPubMed
3.
Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, et al: Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999, 281 (17): 1623-1627. 10.1001/jama.281.17.1623.CrossRefPubMed
4.
Kleinberg L, Forastiere AA: Chemoradiation in the management of esophageal cancer. J Clin Oncol. 2007, 25 (26): 4110-4117. 10.1200/JCO.2007.12.0881.CrossRefPubMed
5.
Kleinberg L, Gibson MK, Forastiere AA: Chemoradiotherapy for localized esophageal cancer: regimen selection and molecular mechanisms of radiosensitization. Nat Clin Pract Oncol. 2007, 4 (5): 282-294. 10.1038/ncponc0796.CrossRefPubMed
6.
Sasaki Y, Amano T, Morita M, Shinkai T, Eguchi K, Tamura T, Ohe Y, Kojima A, Saijo N: Phase I study and pharmacological analysis of cis-diammine (glycolato) platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion. Cancer Res. 1991, 51 (5): 1472-1477.PubMed
7.
Uchida N, Takeda Y, Hojo K, Maekawa R, Sugita K, Yoshioka T: Sequence-dependent antitumour efficacy of combination chemotherapy of nedaplatin, a novel platinum complex, with 5-fluorouracil in an in vivo murine tumour model. Eur J Cancer. 1998, 34 (11): 1796-1801. 10.1016/S0959-8049(98)00194-4.CrossRefPubMed
8.
Kameyama Y, Okazaki N, Nakagawa M, Koshida H, Nakamura M, Gemba M: Nephrotoxicity of a new platinum compound, 254-S, evaluated with rat kidney cortical slices. Toxicol Lett. 1990, 52 (1): 15-24. 10.1016/0378-4274(90)90161-E.CrossRefPubMed
9.
Grunberger B, Raderer M, Schmidinger M, Hejna M: Palliative chemotherapy for recurrent and metastatic esophageal cancer. Anticancer Res. 2007, 27 (4C): 2705-2714.PubMed
10.
Muro K, Hamaguchi T, Ohtsu A, Boku N, Chin K, Hyodo I, Fujita H, Takiyama W, Ohtsu T: A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer. Ann Oncol. 2004, 15 (6): 955-959. 10.1093/annonc/mdh231.CrossRefPubMed
11.
Taguchi T, Wakui A, Nabeya K, Kurihara M, Isono K, Kakegawa T, Ota K: [A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. 254-S Gastrointestinal Cancer Study Group]. Gan To Kagaku Ryoho. 1992, 19 (4): 483-488.PubMed
12.
Sato Y, Takayama T, Sagawa T, Okamoto T, Miyanishi K, Sato T, Araki H, Iyama S, Abe S, Murase K, et al: A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer. Cancer Chemother Pharmacol. 2006, 58 (5): 570-576. 10.1007/s00280-006-0193-x.CrossRefPubMed
13.
Kodaira T, Fuwa N, Kamata M, Furutani K, Tachibana H, Yamazaki T: Single-institute phase I/II trial of alternating chemoradiotherapy with 5-FU and nedaplatin for esophageal carcinoma. Anticancer Res. 2006, 26 (1B): 471-478.PubMed
14.
Ishikura S, Ohtsu A, Shirao K, Muro K, Kagami Y, Nihei K, Mera K, Ito Y, Boku N, Yoshida S: A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with T4 esophageal cancer: Japan Clinical Oncology Group trial (JCOG 9908). Esophagus. 2005, 2: 133-137. 10.1007/s10388-005-0055-3.CrossRef
15.
O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA: Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994, 331 (8): 502-507. 10.1056/NEJM199408253310803.CrossRefPubMed
16.
Lawrence TS, Tepper JE, Blackstock AW: Fluoropyrimidine-Radiation Interactions in Cells and Tumors. Semin Radiat Oncol. 1997, 7 (4): 260-266. 10.1016/S1053-4296(97)80024-0.CrossRefPubMed
17.
Begg AC: Cisplatin and radiation: interaction probabilities and therapeutic possibilities. Int J Radiat Oncol Biol Phys. 1990, 19 (5): 1183-1189.CrossRefPubMed
18.
Yang LX, Douple EB, O'Hara JA, Wang HJ: Carboplatin enhances the production and persistence of radiation-induced DNA single-strand breaks. Radiat Res. 1995, 143 (3): 302-308. 10.2307/3579217.CrossRefPubMed
19.
Cividalli A, Ceciarelli F, Livdi E, Altavista P, Cruciani G, Marchetti P, Danesi DT: Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule. Int J Radiat Oncol Biol Phys. 2002, 52 (4): 1092-1098.CrossRefPubMed
20.
Tahara M, Ohtsu A, Hironaka S, Boku N, Ishikura S, Miyata Y, Ogino T, Yoshida S: Clinical impact of criteria for complete response (CR) of primary site to treatment of esophageal cancer. Jpn J Clin Oncol. 2005, 35 (6): 316-323. 10.1093/jjco/hyi095.CrossRefPubMed
21.
Ohtsu A, Boku N, Muro K, Chin K, Muto M, Yoshida S, Satake M, Ishikura S, Ogino T, Miyata Y, et al: Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol. 1999, 17 (9): 2915-2921.PubMed
22.
Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP: 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): 1167-1174. 10.1200/JCO.20.5.1167.CrossRefPubMed
23.
Hironaka S, Ohtsu A, Boku N, Muto M, Nagashima F, Saito H, Yoshida S, Nishimura M, Haruno M, Ishikura S, et al: Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2-3)N(any) M(0) squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys. 2003, 57 (2): 425-433. 10.1016/S0360-3016(03)00585-6.CrossRefPubMed
24.
Ishida K, Ando N, Yamamoto S, Ide H, Shinoda M: Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516). Jpn J Clin Oncol. 2004, 34 (10): 615-619. 10.1093/jjco/hyh107.CrossRefPubMed
25.
Rich TA, Ajani JA, Morrison WH, Ota D, Levin B: Chemoradiation therapy for anal cancer: radiation plus continuous infusion of 5-fluorouracil with or without cisplatin. Radiother Oncol. 1993, 27 (3): 209-215. 10.1016/0167-8140(93)90076-K.CrossRefPubMed
26.
Schaake-Koning C, Bogaert van den W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, et al: Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992, 326 (8): 524-530.CrossRefPubMed
27.
Itoh Y, Fuwa N: Retrospective analysis: concurrent chemoradiotherapy using protracted continuous infusion of low-dose cisplatin and 5-fluorouracil for T2N0 glottic cancer. Radiat Med. 2006, 24 (4): 277-281. 10.1007/s11604-005-1517-1.CrossRefPubMed
28.
Sasamoto R, Sakai K, Inakoshi H, Sueyama H, Saito M, Sugita T, Tsuchida E, Ito T, Matsumoto Y, Yamanoi T, et al: Long-term results of chemoradiotherapy for locally advanced esophageal cancer, using daily low-dose 5-fluorouracil and cis-diammine-dichloro-platinum (CDDP). Int J Clin Oncol. 2007, 12 (1): 25-30. 10.1007/s10147-006-0617-y.CrossRefPubMed
29.
Sai H, Mitsumori M, Yamauchi C, Araki N, Okumura S, Nagata Y, Nishimura Y, Hiraoka M: Concurrent chemoradiotherapy for esophageal cancer: comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil. Int J Clin Oncol. 2004, 9 (3): 149-153. 10.1007/s10147-004-0385-5.CrossRefPubMed
30.
Nishimura Y, Mitsumori M, Hiraoka M, Koike R, Nakamatsu K, Kawamura M, Negoro Y, Fujiwara K, Sakurai H, Mitsuhashi N: A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021). Radiother Oncol. 2009, 92 (2): 260-265. 10.1016/j.radonc.2008.12.012.CrossRefPubMed
31.
Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J: Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007, 8 (3): 226-234. 10.1016/S1470-2045(07)70039-6.CrossRefPubMed
32.
Mariette C, Piessen G, Triboulet JP: Therapeutic strategies in oesophageal carcinoma: role of surgery and other modalities. Lancet Oncol. 2007, 8 (6): 545-553. 10.1016/S1470-2045(07)70172-9.CrossRefPubMed
33.
Avery KN, Metcalfe C, Barham CP, Alderson D, Falk SJ, Blazeby JM: Quality of life during potentially curative treatment for locally advanced oesophageal cancer. Br J Surg. 2007, 94 (11): 1369-1376. 10.1002/bjs.5888.CrossRefPubMed
34.
Lagergren P, Avery KN, Hughes R, Barham CP, Alderson D, Falk SJ, Blazeby JM: Health-related quality of life among patients cured by surgery for esophageal cancer. Cancer. 2007, 110 (3): 686-693. 10.1002/cncr.22833.CrossRefPubMed
35.
Ishikura S, Nihei K, Ohtsu A, Boku N, Hironaka S, Mera K, Muto M, Ogino T, Yoshida S: Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003, 21 (14): 2697-2702. 10.1200/JCO.2003.03.055.CrossRefPubMed
36.
Kumekawa Y, Kaneko K, Ito H, Kurahashi T, Konishi K, Katagiri A, Yamamoto T, Kuwahara M, Kubota Y, Muramoto T, et al: Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma. J Gastroenterol. 2006, 41 (5): 425-432. 10.1007/s00535-006-1771-8.CrossRefPubMed
37.
Inaba H, Tsuda T, Miyazaki A, Watanabe Y, Nakaya S, Koitabashi Y, Ogihara K, Hara T, Kato N, Kobayashi Y, et al: [Clinical study of the combination of small amount of nedaplatin (CDGP)/5-FU with radiation for the treatment of esophageal cancer]. Nippon Shokakibyo Gakkai Zasshi. 2002, 99 (10): 1191-1196.PubMed
38.
Kato H, Fukuchi M, Manda R, Nakajima M, Miyazaki T, Sohda M, Masuda N, Fukai Y, Tsukada K, Kuwano H: Efficacy and toxicity of nedaplatin and 5-FU with radiation treatment for advanced esophageal carcinomas. Anticancer Res. 2003, 23 (4): 3493-3498.PubMed
39.
Yamanaka H, Motohiro T, Michiura T, Asai A, Mori T, Hioki K: Nedaplatin and 5-FU combined with radiation in the treatment for esophageal cancer. Jpn J Thorac Cardiovasc Surg. 1998, 46 (10): 943-948.CrossRefPubMed
40.
Nemoto K, Matsushita H, Ogawa Y, Takeda K, Takahashi C, Britton KR, Takai Y, Miyazaki S, Miyata T, Yamada S: Radiation therapy combined with cis-diammine-glycolatoplatinum (Nedaplatin) and 5-fluorouracil for untreated and recurrent esophageal cancer. Am J Clin Oncol. 2003, 26 (1): 46-49. 10.1097/00000421-200302000-00010.CrossRefPubMed
41.
Yamashita H, Nakagawa K, Tago M, Igaki H, Nakamura N, Shiraishi K, Sasano N, Ohtomo K: Radiation therapy combined with cis-diammine-glycolatoplatinum (nedaplatin) and 5-fluorouracil for Japanese stage II-IV esophageal cancer compared with cisplatin plus 5-fluorouracil regimen: a retrospective study. Dis Esophagus. 2006, 19 (1): 15-19. 10.1111/j.1442-2050.2006.00531.x.CrossRefPubMed
42.
Jingu K, Nemoto K, Matsushita H, Takahashi C, Ogawa Y, Sugawara T, Nakata E, Takai Y, Yamada S: Results of radiation therapy combined with nedaplatin (cis-diammine-glycoplatinum) and 5-fluorouracil for postoperative locoregional recurrent esophageal cancer. BMC Cancer. 2006, 6: 50-10.1186/1471-2407-6-50.CrossRefPubMedPubMedCentral
Metadata
Title
Prospective study of daily low-dose nedaplatin and continuous 5-fluorouracil infusion combined with radiation for the treatment of esophageal squamous cell carcinoma
Authors
Satoshi Osawa
Takahisa Furuta
Ken Sugimoto
Takashi Kosugi
Tomohiro Terai
Mihoko Yamade
Yasuhiro Takayanagi
Masafumi Nishino
Yasushi Hamaya
Chise Kodaira
Takanori Yamada
Moriya Iwaizumi
Kosuke Takagaki
Ken-ichi Yoshida
Shigeru Kanaoka
Mutsuhiro Ikuma
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-408

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