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. 1999 Jun;80(7):1052–1057. doi: 10.1038/sj.bjc.6690462

Phase I study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced oesophageal cancer

A van der Gaast 1, T C Kok 1, L Kerkhofs 1, P D Siersema 2, H W Tilanus 3, T A W Splinter 1
PMCID: PMC2363040  PMID: 10362115

Abstract

We performed this dose-finding study with a fixed dose of cisplatin and increasing doses of paclitaxel given every 2 weeks to determine the maximum tolerable dose of this schedule. Sixty-four patients with advanced oesophageal cancer were treated with a cisplatin dose of 60 mg m−2 and increasing doses of paclitaxel from 100 mg m−2 up to 200 mg m−2 both administered over 3 h for a maximum of six cycles in patients with stable disease or eight cycles in responding patients. Patients were retreated when the granulocytes were > 0.75 × 109 l−1 and the platelets > 75 × 109 l−1. The dose of paclitaxel could be increased to 200 mg m−2 without encountering dose limiting haematological toxicity. At the dose levels 190 mg m−2 and 200 mg m−2 of paclitaxel cumulative sensory neurotoxicity became the dose-limiting toxicity. The dose intensity of paclitaxel calculated over six cycles rose from 50 mg m−2 per week to 85 mg m−2 per week. Only three episodes of granulocytopenic fever were encountered out of a total of 362 cycles of treatment. Of the 59 patients evaluable for response, 31 (52%) had a partial or complete response. In a biweekly schedule with a fixed dose of 60 mg m−2 cisplatin it is possible to increase the dose of paclitaxel to 180 mg m−2. At higher dose levels, neurotoxicity becomes the dose-limiting toxicity. The observed response rate warrants further investigation of this schedule. © 1999 Cancer Research Campaign

Keywords: oesophageal cancer, cisplatin, paclitaxel, biweekly schedule

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Selected References

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  1. Ajani J. A., Ilson D. H., Daugherty K., Pazdur R., Lynch P. M., Kelsen D. P. Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst. 1994 Jul 20;86(14):1086–1091. doi: 10.1093/jnci/86.14.1086. [DOI] [PubMed] [Google Scholar]
  2. Ajani J. A., Ilson D. H., Kelsen D. P. Paclitaxel in the treatment of patients with upper gastrointestinal carcinomas. Semin Oncol. 1996 Oct;23(5 Suppl 12):55–58. [PubMed] [Google Scholar]
  3. Connelly E., Markman M., Kennedy A., Webster K., Kulp B., Peterson G., Belinson J. Paclitaxel delivered as a 3-hr infusion with cisplatin in patients with gynecologic cancers: unexpected incidence of neurotoxicity. Gynecol Oncol. 1996 Aug;62(2):166–168. doi: 10.1006/gyno.1996.0210. [DOI] [PubMed] [Google Scholar]
  4. Daly J. M., Karnell L. H., Menck H. R. National Cancer Data Base report on esophageal carcinoma. Cancer. 1996 Oct 15;78(8):1820–1828. doi: 10.1002/(sici)1097-0142(19961015)78:8<1820::aid-cncr25>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  5. Eisenhauer E. A., ten Bokkel Huinink W. W., Swenerton K. D., Gianni L., Myles J., van der Burg M. E., Kerr I., Vermorken J. B., Buser K., Colombo N. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994 Dec;12(12):2654–2666. doi: 10.1200/JCO.1994.12.12.2654. [DOI] [PubMed] [Google Scholar]
  6. Fennelly D., Aghajanian C., Shapiro F., O'Flaherty C., McKenzie M., O'Connor C., Tong W., Norton L., Spriggs D. Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer. J Clin Oncol. 1997 Jan;15(1):187–192. doi: 10.1200/JCO.1997.15.1.187. [DOI] [PubMed] [Google Scholar]
  7. Gelmon K. A., O'Reilly S. E., Tolcher A. W., Campbell C., Bryce C., Ragaz J., Coppin C., Plenderleith I. H., Ayers D., McDermott B. Phase I/II trial of biweekly paclitaxel and cisplatin in the treatment of metastatic breast cancer. J Clin Oncol. 1996 Apr;14(4):1185–1191. doi: 10.1200/JCO.1996.14.4.1185. [DOI] [PubMed] [Google Scholar]
  8. Gordon A. N., Stringer C. A., Matthews C. M., Willis D. L., Nemunaitis J. Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer receiving cisplatin: rapid development of neurotoxicity is dose-limiting. J Clin Oncol. 1997 May;15(5):1965–1973. doi: 10.1200/JCO.1997.15.5.1965. [DOI] [PubMed] [Google Scholar]
  9. 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 Jun 11;326(24):1593–1598. doi: 10.1056/NEJM199206113262403. [DOI] [PubMed] [Google Scholar]
  10. Hilkens P. H., van der Burg M. E., Moll J. W., Planting A. S., van Putten W. L., Vecht C. J., van den Bent M. J. Neurotoxicity is not enhanced by increased dose intensities of cisplatin administration. Eur J Cancer. 1995;31A(5):678–681. doi: 10.1016/0959-8049(94)00497-s. [DOI] [PubMed] [Google Scholar]
  11. Kok T. C. Chemotherapy in oesophageal cancer. Cancer Treat Rev. 1997 Mar;23(2):65–85. doi: 10.1016/s0305-7372(97)90021-9. [DOI] [PubMed] [Google Scholar]
  12. Kok T. C., Van der Gaast A., Dees J., Eykenboom W. M., Van Overhagen H., Stoter G., Tilanus H. W., Splinter T. A. Cisplatin and etoposide in oesophageal cancer: a phase II study. Rotterdam Oesophageal Tumour Study Group. Br J Cancer. 1996 Sep;74(6):980–984. doi: 10.1038/bjc.1996.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McGuire W. P., Hoskins W. J., Brady M. F., Kucera P. R., Partridge E. E., Look K. Y., Clarke-Pearson D. L., Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1–6. doi: 10.1056/NEJM199601043340101. [DOI] [PubMed] [Google Scholar]
  14. O'Reilly S., Forastiere A. A. Is surgery necessary with multimodality treatment of oesophageal cancer. Ann Oncol. 1995 Jul;6(6):519–521. doi: 10.1093/oxfordjournals.annonc.a059237. [DOI] [PubMed] [Google Scholar]
  15. Rowinsky E. K., Cazenave L. A., Donehower R. C. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst. 1990 Aug 1;82(15):1247–1259. doi: 10.1093/jnci/82.15.1247. [DOI] [PubMed] [Google Scholar]
  16. Rowinsky E. K., Chaudhry V., Forastiere A. A., Sartorius S. E., Ettinger D. S., Grochow L. B., Lubejko B. G., Cornblath D. R., Donehower R. C. Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol. 1993 Oct;11(10):2010–2020. doi: 10.1200/JCO.1993.11.10.2010. [DOI] [PubMed] [Google Scholar]
  17. Sparano J. A., Neuberg D., Glick J. H., Robert N. J., Goldstein L. J., Sledge G. W., Wood W. Phase II trial of biweekly paclitaxel and cisplatin in advanced breast carcinoma: an Eastern Cooperative Oncology Group study. J Clin Oncol. 1997 May;15(5):1880–1884. doi: 10.1200/JCO.1997.15.5.1880. [DOI] [PubMed] [Google Scholar]
  18. Swenerton K., Hoskins P., Stuart G., Batist G., Pike J., Onetto N., Fisher B., Eisenhauer E. A phase I study of bi-weekly paclitaxel/cisplatin as initial therapy for advanced ovarian cancer. A study of the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 1996 Dec;7(10):1077–1079. doi: 10.1093/oxfordjournals.annonc.a010502. [DOI] [PubMed] [Google Scholar]

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