Abstract
Paclitaxel represents a novel antitumour agent with demonstrated activity in cisplatin-sensitive tumours, particularly ovarian cancer. In addition, responses to pacliaxel have been observed in patients with cisplatin-refractory ovarian cancer. The role of paclitaxel in the treatment of testicular cancer has not been explored so far. Despite the generally high cure rates in patients with metastatic testicular cancer, patients with relapsed disease not responding to platin-based salvage chemotherapy have an extremely poor prognosis. In a phase I/II trial 10 patients with relapsed, cisplatin-refractory malignant germ-cell tumours were treated with paclitaxes as 6-h infusions (8 patients) or 3-h infusions (2 patients) at doses from 135 mg/m2 to 310 mg/m2 at 3-week intervals. Three patients achieved a response to paclitaxel, but disease recurred shortly in two patients after two and four cycles of therapy, respectively. One patient has remained in marker-negative partial reponse for more than 5 months. The toxicity of paclitaxel was tolerable for a dose range from 135 mg/m2 to 225 mg/m2. Granulocytopenia, WHO grades 3 and 4, occurred in all patients but was of short duration (median 3 days; range: 2–7 days). Other toxicities such as mucositis (5 patients grade 1), neurotoxicity (1 patient grade 1, 1 patients grade 2), infection (1 patient grade 3) and diarrhoea (1 patient grade 2) were not dose-limiting. There were no hypersensitivity reactions, but 1 patient developed severe myalgias during therapy with paclitaxel. Six patients with documented cisplatin-refractory disease were retreated with cisplatin-based chemotherapy after paclitaxel treatment and, in 4 of these, tumour responses of 3, 4, 5 and more than 5 months duration were achieved. In order to explore the role of paclitaxel in relapsed and/or cisplatin-refractory testicular cancer a phase II study using a 3-h infusion of 225 mg/m2 paclitaxel every 3 weeks, conducted by the German Testicular Cancer Study Group, is ongoing.
Key words: Testicular cancer, Chemotherapy, Cisplatin resistance, Paclitaxel
Footnotes
For the German testicular cancer study group (headed by H.-J. Schmoll and L. Weißbach)
References
- Bokemeyer C, Droz JP, Hanauske A, Schröder M, Queißer W, Schmoll HJ (1993) Treatment of relapsed germ cell tumours with vinorelbine: a trial of the phase I/II-study group of the Association for Medical Oncology of the German cancer society. Onkologie 16:29–31 [Google Scholar]
- Brown T, Havlin K, Weiss G, Cagnola J, Koeller J, Kuhn J, Rizzo J, Craig J, Phillips J, Hoff D van (1991) A phase I trial of taxol given by a 6-hour intravenous infusion. J Clin Oncol 9:1261–1267 [DOI] [PubMed] [Google Scholar]
- Chao CCK, Lee YL, Cheng PW, Lin-Chao S (1991) Enhanced host cell reactivation of demaged plasmid DNA in HeLa cells resistant to cisdiamminedichloroplatinum (II). Cancer Res 51:601–605 [PubMed] [Google Scholar]
- Einhorn LH (1990) Treatment of testicular cancer: a new and improved model. J Clin Oncol 8:1777–1781 [DOI] [PubMed] [Google Scholar]
- Hansen HH, Eisenhauer EA, Hansen M, Neijt JP, Piccart MJ, Sessa C, Thigpen JT (1993) New cytostatic drugs in ovarian cancer. Ann Oncol [Suppl 4] 4:63–70 [DOI] [PubMed] [Google Scholar]
- Harstrick A, Schmoll HJ, Wilke H, Schöber C, Stahl M, Köhne-Wömpner C, Bokemeyer C, Dölken G, Burk K, Poliwoda H (1990) Highdose epidoxorubicin in refractory or relapsed nonseminomatous testicular cancer: a phase II study. Ann Oncol 1:375–376 [DOI] [PubMed] [Google Scholar]
- Hill BT, Shellard SA, Whelan RDH, Pera MF, Harstrick A, Fichtinger-Schepman AMJ (1992) Deficient removal of the major platinum-DNA intrastrand crosslinks in the sequences pGpG and pApG appears characteristic of testicular teratoma cell lines derived from tumours from untreated patients and may account for their sensitivity to cisplatin (abstract). Proc Am Soc. Oncol 11:100 [Google Scholar]
- Hutter H, Motzer R, Schwartz L, Fischer P, Bajorin D, Scher H, Bosl G (1994) Phase II trial of taxol in cisplatin-resistant germ cell tumour (GCT) patients (PTS) (abstract). Proc Am Soc Clin Oncol 13:232 [Google Scholar]
- Kohn EC, Sarosy G, Bicher A, Link C, Christian M, Steinberg, SM, Rothenberg M, Adamo DO, Davis P, Ognibene FP, Cunnion RE, Reed E (1994) Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian, cancer. J Natl Cancer Inst 86:18–24 [DOI] [PubMed] [Google Scholar]
- Kris MG, O'Connel JP, Gralla RJ, Wertheim MS, Parente RM, Schiff PB, Young CW (1986) Phase I trial of taxol given as a 3-hour infusion every 21 days. Cancer Treat Rep 70:605–607 [PubMed] [Google Scholar]
- McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DU, Donehower RC (1989) Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 111:273–279 [DOI] [PubMed] [Google Scholar]
- Reed E, Parker RJ, Dabholkar M (1992) Taxol effect on cisplatin-DNA adduct repair in human ovarian cancer cells (abstract). Second National Cancer Institute Workshop on Taxol, Alexandria, Va.
- Rowinsky EK, Cazenave LA, Donehower RC (1990) Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst 82:1247–1259 [DOI] [PubMed] [Google Scholar]
- Schiff PB, Fant J, Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277:655–667 [DOI] [PubMed] [Google Scholar]
- Swenerton K, Eisenhauer E, Bokkel Huinink W ten, Myles J, Mangini C, Burg M van der, Kerr I, Gianni L, Vermoken J, Buser K, Sadura A, Bacon M, Santabarbara P, Onetto N, Canetta J (1993) Taxol in relapsed ovarian cancer: high vs low dose and short vs long infusion (abstract). Proc. Am Soc Clin Oncol 12:256 [Google Scholar]