BOP/VIP - A new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours

Abstract

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours

“…Suggestive evidence to support this notion is provided by observations in poor risk germ cell tumours, where closely spaced cisplatin therapy has been investigated (Ozols et al, 1988;Horwich et al, 1989;Lewis et al, 1991). Early studies with weekly administration of cisplatin were hampered by the side effects which can nowadays be partly prevented (Corder et al, 1977;Randolph et al, 1978).…”

Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours

“…One patient developed a secondary leukaemia, a phenomenon that has been extensively described in germ-cell tumour survivors (Bokemeyer and Schmoll, 1995). Relatively high rates of toxicity-related death have previously been reported in patients treated with dose-dense regimens (Bower et al, 1997;Kaye et al, 1998;Lewis et al, 1991;Horwich et al, 1994Horwich et al, , 1997Harstrick et al, 1991;Germa Lluch et al, 1992. For example, 6.5% and 7% patients died of toxicity after they had received the BOP/VIP-B and the C-BOP-BEP regimens, respectively (Kaye et al, 1998;Horwitch et al, 1997).…”

“…Finally the Medical Research Council and the EORTC have reported the results of a phase III trial that compared a rapidly recycled intensive regimen (BOP/VIP-B) to the standard 4 BEP in 380 patients with poor-prognosis NSGCT (Kaye et al, 1998). Unfortunately, the BOP/VIP-B regimen, which was initially reported to be highly efficient in 91 patients treated in an uncontrolled study (Lewis et al, 1991) did not afford any survival benefit in this randomised study. Possible explanations for these negative results are a higher number of toxicity-related deaths (12 vs 4) and a higher proportion (10% vs 5%) of primary mediastinal NSGCT, notorious for their poor outcome (Fizazi et al, 1998), in the intensive arm.…”

“…In recent years, data have accumulated suggesting that a high cure rate can be achieved in patients with intermediate-and poor-prognosis NSGCT when dose-dense regimens are used (Bower et al, 1997;Kaye et al, 1998;Fizazi and Zelek, 2000;Lewis et al, 1991;Horwich et al, 1994Horwich et al, , 1997Harstrick et al, 1991;Germa Lluch et al, 1992. However, among the studies that have addressed this issue, only a few (Horwich et al, 1997) were designed as 'true' formal phase II studies like the present study, and only one was a randomised trial (Kaye 1998).…”

The changing role of surgery in metastatic non-seminomatous germ cell tumour

“…Currently the overall cure rate for this tumour is of the order of 90% (Loehrer et al, 1988), although for patients with the most advanced metastatic disease, the prospect of cure is somewhat lower, at approximately 40-70% (Lewis et al, 1991). The optimal management strategy for these patients with large volume metastatic disease has not yet been fully defined.…”