High-dose chemotherapy failed to extend PFS in germ cell tumors
Patients with advanced germ cell tumors who received cisplatin, etoposide and bleomycin chemotherapy demonstrated comparable PFS as those who underwent sequential high-dose chemotherapy with stem-cell rescue, according to results of a randomized, phase 2 study.
Andrea Necchi, MD, of the department of medical oncology at Istituto Nazionale dei Tumori, and colleagues evaluated data from 85 patients with advanced germ cell tumors who had a poor prognosis.
Researchers assigned 43 patients to receive four cycles of cisplatin, etoposide and bleomycin (PEB) chemotherapy every 3 weeks. The other 42 patients received two PEB cycles followed by a high-dose sequence of cyclophosphamide, cisplatin, etoposide with stem-cell support and carboplatin. These patients then underwent autologous stem cell transplantation.
PFS served as the primary endpoint.
Median follow-up was 114.2 months (interquartile range, 87.7-165.8).
Researchers reported overall response rates of 65.1% (95% CI, 49.1-79) in the PEB arm and 69.1% (95% CI, 52.9-82.4) in the high-dose sequence arm. The difference was not statistically significant (
A similar proportion of patients in the PEB and high-dose sequence arms achieved 5-year PFS (55.8% vs. 54.8%;
Multivariate analyses indicated the presence of liver, bone and brain metastases was significantly associated with PFS (HR=2.21; 95% CI, 1.04-4.7).
More patients in the high-dose sequence arm experienced grade 3 to grade 4 infection/sepsis (90.1% vs. 6.9%), gastrointestinal toxicity (59.6% vs. 11.6%) and neurologic toxicity (9.5% vs. 2.3%). One patient in the PEB arm died due to a treatment-related adverse event.
“These results represent a further step toward the allocation of high-dose chemotherapy in the therapeutic strategy of germ cell tumors,” Necchi and colleagues wrote. “Until new drugs or new concepts become available, further attempts using high-dose chemotherapy to improve response in this patient category should be discouraged.”
Disclosure: The researchers report no relevant financial disclosures.