Abstract
The antitumor efficacy of the combination of nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using human ovarian cancer models. Since NDP has been found to have greater anti‐tumor activity and lower nephrotoxicity than cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM. Increasing doses of NDP (16.5, 33 and 66 mg/kg as a total dose) and a fixed amount of CPM (174 or 348 mg/kg as a total dose) were injected three times at intervals of 7 days via the tail vein into mice implanted with RMUG‐S, OC9‐JCK or KF‐28 human ovarian cancer. Simultaneous administration of NDP with CPM resulted in markedly enhanced inhibition of tumor growth for all cancers tested. The growth inhibition and survival effect of the combination therapy of NDP with CPM against KF‐28 and OC9‐JCK were as potent as those of CDDP plus CPM. Neither increased hematotoxicity nor a significant difference in maximum concentration, half time or area under the curve of platinum or CPM in plasma between the single and combined treatment was found. These results suggest that the combination of NDP with CPM may be clinically effective.
Keywords: Nedaplatin, Cisplatin, Cyclophosphamide, Combination chemotherapy, Ovarian cancer
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REFERENCES
- 1).Totani , T. , Aono , K. , Komura , M. and Adachi , Y.Synthesis of (glycolato‐O, O′)diammineplatinum (II) and its related complexes . Chem. Lett. , 3 , 429 – 432 ( 1986. ). [Google Scholar]
- 2).Suzumura , S. , Kato , T. , Ueda , R. and Ohta , K.Effect of treatment schedule on antitumor activity of glycolato‐O, O′‐diammineplatinum (II), a new platinum derivative: comparison with cis‐diamminedichloroplatinum (II) . Anticancer Res. , 9 , 1083 – 1088 ( 1989. ). [PubMed] [Google Scholar]
- 3).Shiratori , O. , Kasai , H. , Uchida , N. , Takeda , Y. , Totani , T. and Sato , K.Anti‐tumor activity of 254‐S, a platinum complex, in rodents . In “ Recent Advances in Chemotherapy ” ed. Ishigami J. , pp . 635 – 636 ( 1985. ). University of Tokyo Press; , Tokyo . [Google Scholar]
- 4).Koenuma , M. , Kasai , H. , Uchida , N. , Wada , T. , Hattori , M. , Oguma , T. , Totani , T. and Inaba , M.Pharmacokinetic correlation between experimental and clinical effects on human non‐small cell lung cancers of cis‐diammine glycolatoplatinum (254‐S) and cis‐diammine dichloroplatinum . Anticancer Res. , 15 , 417 – 422 ( 1995. ). [PubMed] [Google Scholar]
- 5).Kameyama , Y. , Okazaki , N. , Nakagawa , M. , Koshida , H. , Nakamura , M. and Gemba , M.Nephrotoxicity of a new platinum compound, 254‐S, evaluated with rat kidney cortical slices . Toxicol. Lett. , 52 , 15 – 24 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 6).Furuse , K. , Fukuoka , M. , Ohshima , S. , Ariyoshi , Y. , Fujii , M. , Kurita , Y. , Hasegawa , K. , Homma , T. , Tamura , M. , Inoue , S. , Nishiwaki , Y. , Kimura , I. and Niitani , H.Phase II clinical study of (glycolato‐O, O′)diammineplatinum (II), a new platinum complex, for primary lung cancer . Proc. Am. Soc. Clin. Oncol. , 8 , 238 ( 1989. ). [Google Scholar]
- 7).Fukuda , M. , Shinkai , T. , Eguchi , K. , Sasaki , Y. , Tamura , T. , Ohe , Y. , Kojima , A. , Oshita , F. , Hara , K. and Saijo , N.Phase II study of (glycolato‐O, O′)diammineplatinum (II), a novel platinum complex, in the treatment of non‐small‐cell lung cancer . Cancer Chemother. Pharmacol. , 26 , 393 – 396 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 8).Inuyama , Y. , Miyake , H. , Horiuchi , M. , Hayasaki , K. , Komiyama , S. and Ohta , K.An early phase II study of cis‐diammine glycolato platinum, 254‐S, for head and neck cancers . Jpn. J. Cancer Chemother. , 19 , 863 – 869 ( 1992. ). [PubMed] [Google Scholar]
- 9).Akaza , H. , Togashi , M. , Nishio , Y. , Miki , T. , Kotake , T. , Matumura , Y. , Yoshida , O. and Aso , Y.Phase II study of cis‐diammine(glycolato)platinum, 254‐S, in patients with advanced germ‐cell testicular cancer, prostatic cancer, and transitional‐cell carcinoma of the urinary tract . Cancer Chemother. Pharmacol. , 31 , 187 – 192 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 10).Kato , T. , Noda , K. , Hirabayashi , K. and Nishimura , H.Phase II study of cis‐diammine(glycolato)platinum (254‐S), a new platinum complex, for gynecological malignancy . Proc. 16th Int. Congr. Chemother., Anticancer Sect. , 823 , 1 – 2 ( 1989. ). [Google Scholar]
- 11).Uchida , N. , Kasai , H. , Takeda , Y. , Maekawa , R. , Sugita , K. and Yoshioka , T.Augmented antitumor activity in combination chemotherapy of Nedaplatin with Etoposide . Anticancer Res. , 18 , 247 – 252 ( 1998. ). [PubMed] [Google Scholar]
- 12).Uchida , N. , Takeda , Y. , Hojo , K. , Maekawa , R. , Sugita , K. and Yoshioka , T.Sequence‐dependent antitumor efficacy of combination chemotherapy of Nedaplatin, a novel platinum complex, with 5‐Fluorouracil on in vivo murine tumor model . Eur. J. Cancer , 34 , 1796 – 1801 ( 1998. ). [DOI] [PubMed] [Google Scholar]
- 13).Ozols , R. F. and Young , R. C.Chemotherapy of ovarian cancer . Semin. Oncol. , 18 , 222 – 232 ( 1991. ). [PubMed] [Google Scholar]
- 14).Pronzato , P. , Bertelli , G. , Vigani , A. and Vaira , F.A feasibility study of accelerated polychemotherapy with cisplatin, epidoxorubicin and cyclophosphamide (PEC) in advanced ovarian cancer . Br. J. Cancer , 73 , 1425 – 1427 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15).McGuire , W. P. , Hoskins , W. J. , Brady , M. F. , Kucera , P. R. , Partridge , E. E. , Look , K. Y. , Clarke‐Pearson , D. L.and Davidson, M. Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology group) . Semin. Oncol. , 5 , 40 – 47 ( 1996. ). [PubMed] [Google Scholar]
- 16).Bolis , G. , Favalli , G. , Danese , S. , Zanaboni , F. , Mangili , G. , Scarabelli , C. , Tateo , S. , Valsecchi , M. G. , Scarfone , G. , Richiardi , G. , Frigerio , L. , Melpignano , M. , Villa , A. and Parazzini , F.Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given 5 months after cytoreductive surgery for advanced ovarian cancer . J. Clin. Oncol. , 15 , 1938 – 1944 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 17).Gershenson , D. M. , Wharton , J. T. , Copeland , L. J. , Stringer , D. A. , Edwards , C. L. , Kavanagh , J. J. and Freedman , R. S.Treatment of advanced epithelial ovarian cancer with cisplatin and cyclophosphamide . Gynecol. Oncol. , 32 , 336 – 341 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 18).Zambetti , M. , Gianni , L. , Di Re , F. , Spatti , G. , Fontanelli , R. , Escobedo , A. , De Palo , G. and Bonadonna , G.Cisplatin and cyclophosphamide in advanced ovarian carcinoma: activity and toxicity of ambulatory regimen . Am. J. Oncol. 13 , 199 – 203 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 19).Tibben , J. G. , Schijf , C. P. T. and Beex , L. V. A. M.Results of cyclophosphamide and cisplatin combination chemotherapy in patients with ovarian carcinoma . Eur. J. Gynaecol. Oncol. , 13 , 331 – 339 ( 1992. ). [PubMed] [Google Scholar]
- 20).McGuire , W. P. , Hoskins , W. J. , Brady , M. F. , Kucera , P. R. , Partridge , E. E. , Look , K. Y. , Clarke‐Pearson , D. L. and Davidson , M.Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group) . Semin. Oncol. , 5 , 40 – 47 ( 1996. ). [PubMed] [Google Scholar]
- 21).Uchida , N. , Takeda , Y. , Kasai , H. , Maekawa , R. , Sugita , K. and Yoshioka , T.Antitumor efficacy of Nedaplatin, a novel platinum complex, with cyclophosphamide in murine and human tumor model . Anticancer Res. , 18 , 3375 – 3379 ( 1998. ). [PubMed] [Google Scholar]
- 22).Kudoh , K. , Kikuchi , Y. , Hiramatsu , J. , Hirata , J. , Yamamoto , K. , Kita , T. and Nagata , I.Enhancement of antitumor activity of cisplatin by N, N‐diethyl‐2‐[4‐(phenyl‐methyl)phenoxy] ethanamine‐HCl in human ovarian cancer cells with intrinsic or acquired resistance to cisplatin . Eur. J. Cancer , 33 , 122 – 128 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 23).Wallenstein , S. , Zucker , C. L. and Fleis , J. L.Some statistical methods useful in circulation research . Circ. Res. , 47 , 1 – 9 ( 1980. ). [DOI] [PubMed] [Google Scholar]
- 24).Dunnett , C. W.New tables for multiple comparisons with a control . Biometrics , 20 , 482 – 491 ( 1964. ). [Google Scholar]
- 25).Ikeuchi , I. and Amano , T.Fluorometric determination of 4‐hydroxyifosfamide in blood and urine . Chem. Pharm. Bull. , 33 , 2416 – 2420 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 26).Alley , M. C. , Scudiero , D. A. , Monks , A. , Hersey , M. L. , Czerwinski , M. J. , Fine , D. L. , Abott , B. J. , Mayo , J. G. , Shoemaker , R. H. and Boyd , M. R.Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay . Cancer Res. , 48 , 589 – 601 ( 1988. ). [PubMed] [Google Scholar]
- 27).Neijet , J. P. , ten Bokkel Huinink , W. W. , ven der Burg , M. E. L. , Van Oosterom , A. T. , Vriesendorp , R. , Kooyman , C. D. , Van Lindert , A. C. M. , Hamerlynck , J. V. T. H. , Van Lent , M. , Van Houwelingen , J. C. and Pinedo , H. M.Ran domized trial comparing two combination chemotherapy regimens (HEXA‐CAF vs CHAP‐5) in advanced ovarian cancer . Lancet , ii , 594 – 600 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 28).Omura , G. A. , Blessing , J. A. , Ehrlich , C. E. , Miller , A. , Yordan , E. , Creasman , W. T. and Homesley , H. D.A ran domized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian cancer . Cancer , 57 , 1725 – 1730 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 29).Reed , E. , Kohn , E. C. , Sarosy , G. , Dabholker , M. , Davis , P. , Jacob , J. and Maher , M.Paclitaxicel, cisplatin, and cyclo‐phosphamide in human ovarian cancer: molecular rationale and early clinical results . Semin. Oncol. , 22 , 90 – 96 ( 1995. ). [PubMed] [Google Scholar]
- 30).Lartigue‐Mattei , C. , Chabard , J. L. , Touzet , C. , Chollet , P. , Plagne , R. , Petit , J. and Berger , J. A.Pharmacokinetics of cyclophosphamide administered alone or in combination with vindesin or cisplatin in 5 patients with bronchial adenocarcinoma . Biomed. Pharmacother. , 42 , 555 – 560 ( 1988. ). [PubMed] [Google Scholar]