Abstract
Purpose
To define the most effective combination schedule of paclitaxel and nedaplatin, a new platinum derivative, we investigated the in vitro interaction between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1 esophageal squamous carcinoma cell lines.
Materials and methods
Cytotoxic activity was determined by the WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism using a quantitative method based on the median-effect principle of Chou and Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow cytometry.
Results
Upon 24-h sequential exposure, the sequence paclitaxel followed by nedaplatin induced greater than additive effects in all of the cell lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast, antagonistic effects were observed with the reverse sequence. Simultaneous treatment resulted in either a synergistic or antagonistic effect, depending on the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears most active, at least in these three cell lines. Flow cytometric analyses at IC50 indicated that paclitaxel induced G2/M arrest with subsequent induction of apoptosis (56%) in the sub-G1 phase. When paclitaxel preceded nedaplatin, apoptosis was most prominent (70%) with pronounced G2/M arrest. By contrast, the reverse sequence yielded only 28% induction of apoptotic cells, with almost identical cell-cycle distribution patterns to those observed with nedaplatin alone, indicating that the activity of paclitaxel is abolished by pretreatment with nedaplatin.
Conclusions
Our findings suggest that the interaction of nedaplatin and paclitaxel is highly schedule dependent and that the sequential administration of paclitaxel followed by nedaplatin should be thus incorporated into the design of a clinical trial.
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References
Ajani JA, Ilson DH, Daugherty K, Pazdur R, Lynch PM, Kelsen DP (1994) Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst 86:1086–1091
Alberts DS, Fanta PT, Running KL, Adair LP Jr, Garcia DJ, Liu-Stevens R, Salmon SE (1997) In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers. Cancer Chemother Pharmacol 39:493–497
Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27–55
Chou TC, Motzer RJ, Tong V, Bosl GJ (1994) Computerized quantitation of synergism and antagonism of Taxol, topotecan, and cisplatin against human teratocarcinoma cell growth: a rational approach to clinical protocol design. J Natl Cancer Inst (Bethesda) 86:1517–1524
Christen RD, Jekunen AP, Jones JA, Thiebaut F, Shalinsky DR, Howell SB (1993) In vitro modulation of cisplatin accumulation in human ovarian carcinoma cells by pharmacologic alteration of microtubules. J Clin Invest 92:431–440
Forastiere AA, Shank D, Neuberg D, Taylor SG IV, DeConti RC, Adams G (1998) Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial (PA390). Cancer 82:2270–2274
Fukuda M, Shinkai T, Eguchi K, Sasaki Y, Tamura T, Ohe Y, Kojima A, Oshita F, Hara K, Saijo N (1990) Phase II study of (glycolate-O,O’) diammineplatinum(II), a novel platinum complex, in the treatment of non-small-cell lung cancer. Cancer Chemother Pharmacol 26:393–396
Ishiyama M, Shiga M, Sasamoto K, Mizoguchi M, He P (1993) A new sulfonated tetrazolium salt that produces a highly water-soluble formazan dye. Chem Pharm Bull 41:1118
Inuyama Y, Miyake H, Horiuchi M, Hayasaki K, Komiyama S, Ota K (1992) A late phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers. Japanese Gan To Kagaku Ryoho 19:871–877
Kameyama Y, Okazaki N, Nakagawa M, Koshida H, Nakamura M, Gemba M. (1990) Nephrotoxicity of a new platinum compound, 254-S, evaluated with rat kidney cortical slices. Toxicol Lett 52:15–24
Kano Y, Akutsu M, Tsunoda S, Suzuki K, Yazawa Y (1996) In vitro schedule-dependent interaction between paclitaxel and cisplatin in human carcinoma cell lines. Cancer Chemother Pharmacol 37:525–530
Kobayashi H, Takemura Y, Miyachi H, Ogawa T (1991) Antitumor activities of new platinum compounds, DWA2114R, NK121 and 254-S, against human leukemia cells sensitive or resistant to cisplatin. Invest New Drugs 9:313–319
Liebmann JE, Fisher J, Teague D, Cook JA (1994) Sequence dependence of paclitaxel (Taxol) combined with cisplatin or alkylators in human cancer cells. Oncol Res 6:25–31
Ma J, Maliepaard M, Nooter K, Boersma AW, Verweij J, Stoter G, Schellens JH (1998) Synergistic cytotoxicity of cisplatin and topotecan or SN-38 in a panel of eight solid-tumor cell lines in vitro. Cancer Chemother Pharmacol 41:307–316
Matsuoka H, Sugimachi K, Ueo H, Kuwano H, Nakano S, Nakayama M (1987) Sex hormone response of a newly established squamous cell line derived from clinical esophageal carcinoma. Cancer Res 47:4134–4140
McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G (1996) Paclitaxel has moderate activity in squamous cervix cancer. a gynecologic oncology group study. J Clin Oncol 14:792–795
Milross CG, Peters LJ, Hunter NR, Mason KA, Milas L (1995) Sequence-dependent antitumor activity of paclitaxel (taxol) and cisplatin in vivo. Int J Cancer 62:599–604
Noda K, Ikeda M, Yakushiji M, Nishimura H, Terashima Y, Sasaki H, Hata T, Kuramoto H, Tanaka K, Takahashi T et al (1992) A phase II clinical study of cis-diammine glycolato platinum, 254-S, for cervical cancer of the uterus. Japanese Gan To Kagaku Ryoho 19:885–892
Parker RJ, Lee KB, Dabholkar M, Bostick-Bruton F, Simmis M, Reed E (1993) Influence of taxol: cisplatin sequencing on cisplatin-DNA adduct repair in human ovarian cancer cells. Proc Am Assoc Cancer Res 34:356
Rowinsky EK, Citardi MJ, Noe DA, Donehower RC (1993) Sequence-dependent cytotoxic effects due to combinations of cisplatin and the antimicrotubule agents taxol and vincristine. J Cancer Res Clin Oncol 119:727–733
Sakamoto J, Morita S, Yumiba T, Narahara H, Kinoshita K, Nakane Y, Imamoto H, Shiozaki H (2003) Ascitic Gastric Cancer Study Group of the Japan South West Oncology Group. A phase II clinical trial to evaluate the effect of paclitaxel in patients with ascites caused by advanced or recurrent gastric carcinoma: a new concept of clinical benefit response for non-measurable type of gastric cancer. Jpn J Clin Oncol 33:238–240
Sekine I, Nishiwaki Y, Watanabe K, Yoneda S, Saijo N (1996) Phase II study of 3-hour infusion of paclitaxel in previously untreated non-small cell lung cancer. Clin Cancer Res 2:941–945
Sorenson CM, Eastman A (1988) Mechanism of cis-diamminedichloroplatinum (II)-induced cytotoxicity: role of G2 arrest and DNA double-strand breaks. Cancer Res 48:4484–4488
Taguchi T, Wakui A, Nabeya K, Kurihara M, Isono K, Kakegawa T, Ota K (1992) A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. 254-S Gastrointestinal Cancer Study Group. Japanese Gan To Kagaku Ryoho 19:483–488
Tanaka R, Ariyama H, Qin B, Takii Y, Baba E, Mitsugi K, Harada M, Nakano S (2005) In vitro schedule-dependent interaction between Paclitaxel and Oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol (in press)
Yamada H, Uchida N, Maekawa R, Yoshioka T (2001) Sequence-dependent antitumor efficacy of combination chemotherapy with nedaplatin, a newly developed platinum, and paclitaxel. Cancer Lett 172:17–25
Vanhoefer U, Harstrick A, Wilke H, Schleucher N, Walles H, Schroder J, Seeber S (1995) Schedule-dependent antagonism of paclitaxel and cisplatin in human gastric and ovarian carcinoma cell lines in vitro. Eur J Cancer 31A:92–97
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Tanaka, R., Takii, Y., Shibata, Y. et al. In vitro sequence-dependent interaction between nedaplatin and paclitaxel in human cancer cell lines. Cancer Chemother Pharmacol 56, 279–285 (2005). https://doi.org/10.1007/s00280-004-0991-y
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DOI: https://doi.org/10.1007/s00280-004-0991-y