SAN FRANCISCO—Adding the investigational cyclin-dependent kinase inhibitor flavopiridol to FOLFOX combination chemotherapy appears to yield tumor responses in some patients with late-relapse refractory germ cell tumors, suggested authors of a multicenter phase 2 study presented during the 2014 Genitourinary Cancers Symposium.
“Although neither arm met the prespecified endpoint, flavopiridol plus FOLFOX (arm B) was particularly active in late relapse patients, with a 50% overall [Response Evaluation Criteria in Solid Tumors] response rate, including several durable responses,” reported lead author Darren Richard Feldman, MD, of the Memorial Sloan-Kettering Cancer Center in New York, NY, and colleagues.
Following phase 1 evidence of flavopiridol + FOLFOX (leucovorin, 5-fluorouracil [5-FU] and oxaliplatin) activity against refractory germ cell tumors, the authors initiated this phase 2 trial to assess both the efficacy of the regimen and whether or not including 5-FU or leucovorin is necessary, the researchers explained.
A total of 36 previously treated patients participated in the study; all had progressive germ cell tumors and had received (or were not eligible for) high-dose chemotherapy. Of 36 patients, 33 had nonseminoma, they reported. Participants were sequentially assigned to Arm A (n = 7): flavopiridol (70 mg/m2) plus oxaliplatin (86 mg/m2), or Arm B (n = 29): flavopiridol plus FOLFOX, every 2 weeks in 6-week cycles.
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Tumor biopsies before, during, and after treatment were assessed with immunohistochemistry for p53, p21, and cleaved caspase-3, the authors reported.
“Arm A closed early after [zero of seven] patients responded (two SD [stable disease]),” Dr. Feldman and colleagues reported. “Of 25 evaluable patients on Arm B, six achieved a partial response, nine had SD, and 10 had PD [progressive disease].”
“Notably,” the authors reported, five of 10 evaluable late-relapse patients on Arm B had a partial response, including one pathologic complete response, one partial response with negative markers who received radiotherapy for residual bone metastasis, and one partial response with positive markers who received radiotherapy to a residual nodal mass.
“These three patients remain disease-free 19 months [or longer] post-chemotherapy and 17 months [or longer] post-radiotherapy or surgery,” the authors noted.
Median progression-free survival and overall survival were 2.3 months and 7.3 months for all patients, and 3.2 months and 11.2 months for Arm B patients, they reported.
“Further study of FOLFOX with or without flavopiridol is warranted in late relapse patients,” Dr. Feldman concluded.
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).