Despite generally high cure rates in patients with metastatic
germ cell cancer, patients with progressive disease on first-line
cisplatin-based
chemotherapy or with relapsed disease following high-dose
salvage therapy exhibit a very poor prognosis.
Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of
irinotecan in patients with metastatic relapsed or
cisplatin-refractory
germ cell cancer. Refractory disease was defined as progression or relapse within 4 weeks after
cisplatin-based
chemotherapy or relapse after salvage high-dose
chemotherapy with autologous stem cell support.
Irinotecan was administered at a dose of 300 (-350) mg m(-2) every 3 weeks. Response was evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35 (19-53) years. Primary tumour localisation was gonadal/mediastinal in 12/3 patients. Patients had been pretreated with a median of six (4-12)
cisplatin-containing cycles and 13 out of 15 patients had previously failed high-dose
chemotherapy with blood stem cell support. Median number of
irinotecan applications was two (1-3). Fourteen patients are assessable for response and all for toxicity. In one patient, no adequate response evaluation was performed. Toxicity was generally acceptable and consisted mainly of haematological side effects with common toxicity criteria 3 degrees anaemia (two patients), common toxicity criteria 3 degrees
leukocytopenia (one patient) and common toxicity criteria 3 degrees
thrombocytopenia (three patients). Common toxicity criteria 3/4 degrees non-haematological toxicity occurred in five patients (33%): 1 x diarrhoea, 2 x
alopecia, 1 x
fever and in one patient worsening of pre-existing peripheral
polyneuropathy from 1 degrees to 4 degrees. No response was observed to
irinotecan therapy. Currently, 13 patients have died of the disease and two patients are alive with the disease. The patients included in our study exhibit similar prognostic characteristics as patients treated in previous trials evaluating new drugs in this setting.
Irinotecan at a dose of 300-350 mg m(-2) every 3 weeks appears to have no antitumour activity in patients with
cisplatin-refractory
germ cell cancer and, thus, further investigation in this disease is not justified.