Cancer chemotherapy and pharmacology · 2018
A phase II study of NK012, a polymeric micelle formulation of SN-38, in unresectable, metastatic or recurrent colorectal cancer patients.
Клиническое исследование II фазыСтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Hamaguchi Tetsuya, Tsuji Akihito, Yamaguchi Kensei, Takeda Koji, Uetake Hiroyuki, Esaki Taito, Amagai Kenji, Sakai Daisuke, Baba Hideo, Kimura Masami, Matsumura Yasuhiro, Tsukamoto Tetsuji
Аннотация
PURPOSE: NK012 is a polymeric micelle formulation of SN-38, the active metabolite of irinotecan. We evaluated the efficacy and safety of NK012 in Japanese patients with unresectable metastatic colorectal cancer.
METHODS: We conducted a multicenter open-label phase II trial of NK012 monotherapy in 58 patients who had been treated with an oxaliplatin-based chemotherapy regimen (group A: 53 patients with UGT1A1 genotype -/-, *6/-, or *28/-; group B: 5 patients with UGT1A1 genotype *6/*28 or *6/*6). The primary endpoint was the response rate (RR). Initial doses of 28 and 18 mg/m2 for group A and group B, respectively, were administered intravenously over 30 min, and these doses were subsequently administered every 3 weeks. Group A was evaluated as the primary efficacy population, while group B was evaluated for reference.
RESULTS: In group A, the RR was 3.8%, and the median progression-free survival and overall survival were 3.30 months and 15.03 months, respectively. In both groups, the most common grade ≥ 3 adverse drug reaction (ADR) was neutropenia and the incidence of grade ≥ 3 diarrhea was low or zero. In group A, 17 serious ADRs were observed in 10 patients (17%); all improved or recovered. In group B, no serious ADRs were observed. No treatment-related deaths were reported in either group.
CONCLUSIONS: NK012 monotherapy yielded an RR similar to the RR of irinotecan monotherapy that was reported in the phase III EPIC trial (4.2%), and the incidence of grade ≥ 3 diarrhea was low. Based on the incidence and severity of febrile neutropenia and grade ≥ 3 neutropenia, the initial dose of NK012 28 mg/m2 may be too high for colorectal cancer patients who have previously been treated with an oxaliplatin-based chemotherapy regimen.
METHODS: We conducted a multicenter open-label phase II trial of NK012 monotherapy in 58 patients who had been treated with an oxaliplatin-based chemotherapy regimen (group A: 53 patients with UGT1A1 genotype -/-, *6/-, or *28/-; group B: 5 patients with UGT1A1 genotype *6/*28 or *6/*6). The primary endpoint was the response rate (RR). Initial doses of 28 and 18 mg/m2 for group A and group B, respectively, were administered intravenously over 30 min, and these doses were subsequently administered every 3 weeks. Group A was evaluated as the primary efficacy population, while group B was evaluated for reference.
RESULTS: In group A, the RR was 3.8%, and the median progression-free survival and overall survival were 3.30 months and 15.03 months, respectively. In both groups, the most common grade ≥ 3 adverse drug reaction (ADR) was neutropenia and the incidence of grade ≥ 3 diarrhea was low or zero. In group A, 17 serious ADRs were observed in 10 patients (17%); all improved or recovered. In group B, no serious ADRs were observed. No treatment-related deaths were reported in either group.
CONCLUSIONS: NK012 monotherapy yielded an RR similar to the RR of irinotecan monotherapy that was reported in the phase III EPIC trial (4.2%), and the incidence of grade ≥ 3 diarrhea was low. Based on the incidence and severity of febrile neutropenia and grade ≥ 3 neutropenia, the initial dose of NK012 28 mg/m2 may be too high for colorectal cancer patients who have previously been treated with an oxaliplatin-based chemotherapy regimen.