Introduction: Therapy (tp) with IL-2 and IFN-α is considered as an effective immunotp (IT) for mRCC. Bevacizumab (B) proved to have efficacy with different mechanism as regards as IT and had at least an additive effect with chemotherapy (Ch) in many tumors. We searched for a synergism between B, IT and Ch (BIC). Methods: This is a multicenter dose- finding (DF)/phase II study aimed at to investigate: 1) safety and maximum tolerated dose (MTD) of the BIC tp; 2) antitumor activity. DF study comprised 5 escalation dose levels of Ch: Gemcitabine (G) (initial dose [id] 600 mg/m2 to 1,000 mg/m2) followed by 5FU bolus (id 400 mg/m2 to 600 mg/m2) each one on days (d) 1 and 8 every 28 d, associated with fixed doses of B (10 mg/kg on d 1 and 15), IL-2 (1 MUI/m2 bid sc on d 8, 9, 15, 16 and 1 MUI/m2/d sc from d 10 to 12 and from 17 to 19) and IFN-α (3 MUI sc on d 10, 12, 17, 19). DF study was conducted according to Fibonacci statistical method. Phase II study used the reached MTD and was conducted according to two stage Minimax Simon design. Tp was repeated for a maximum of 6 cycles followed by a maintenance with B and IT until progressive disease (PD). Results: 41 pts were enrolled (male 66%); median age 58 yrs; all were assessable for toxicity and 49% were pre-treated. According to MSKCC risk, 27%, 59% and 14% were at low, intermediate and high risk, respectively. Tp was generally well tolerated and MTD was not reached; phase II used the 5° dose level of Ch. Main grade 3-4 toxicity during all cycles: neutropenia non febrile (23/41) and 1 febrile, thrombocytopenia in 11 pts, fever in 7. At present analysis 37 pts are assessable for response: 12 (32%) partial responses (PR), 13 (35%) stable disease and 12 PD for an overall disease control rate (DCR) of 68%; median (med) duration of response was 8.2 mths. In not pre-treated there was a DCR of 78%. Major activity was observed in young pts (< 58 yrs) with a RR of 53% and interesting activity in high MSKCC risk: RR 20% and DCR 80% with a med time to progression (TTP) of 8.7 mths. Overall med TTP was 8.2 mths (CI 95% 6.9-9.4). Conclusions: This is the first study that explored the BIC tp in mRCC and it was generally well tolerated and showed promising activity.
Dose-finding/phase II trial with a combination of bevacizumab (B) plus immunotherapy plus chemotherapy (BIC) in patients with metastatic renal cell cancer (mRCC): A GOIRC multicentre study / Buti, S; Lazzarelli, S; Simonelli, C; Lleshi, A; Lo Re, G; Mattioli, R; Dalla Chiesa, M; Passalacqua, R. - ELETTRONICO. - (2008), pp. 269-269. (Intervento presentato al convegno 2008 American Society of Clinical Oncology (ASCO) Genitourinary Symposium tenutosi a San Francisco, CA, USA nel February 14-16, 2008).
Dose-finding/phase II trial with a combination of bevacizumab (B) plus immunotherapy plus chemotherapy (BIC) in patients with metastatic renal cell cancer (mRCC): A GOIRC multicentre study
Buti S;
2008-01-01
Abstract
Introduction: Therapy (tp) with IL-2 and IFN-α is considered as an effective immunotp (IT) for mRCC. Bevacizumab (B) proved to have efficacy with different mechanism as regards as IT and had at least an additive effect with chemotherapy (Ch) in many tumors. We searched for a synergism between B, IT and Ch (BIC). Methods: This is a multicenter dose- finding (DF)/phase II study aimed at to investigate: 1) safety and maximum tolerated dose (MTD) of the BIC tp; 2) antitumor activity. DF study comprised 5 escalation dose levels of Ch: Gemcitabine (G) (initial dose [id] 600 mg/m2 to 1,000 mg/m2) followed by 5FU bolus (id 400 mg/m2 to 600 mg/m2) each one on days (d) 1 and 8 every 28 d, associated with fixed doses of B (10 mg/kg on d 1 and 15), IL-2 (1 MUI/m2 bid sc on d 8, 9, 15, 16 and 1 MUI/m2/d sc from d 10 to 12 and from 17 to 19) and IFN-α (3 MUI sc on d 10, 12, 17, 19). DF study was conducted according to Fibonacci statistical method. Phase II study used the reached MTD and was conducted according to two stage Minimax Simon design. Tp was repeated for a maximum of 6 cycles followed by a maintenance with B and IT until progressive disease (PD). Results: 41 pts were enrolled (male 66%); median age 58 yrs; all were assessable for toxicity and 49% were pre-treated. According to MSKCC risk, 27%, 59% and 14% were at low, intermediate and high risk, respectively. Tp was generally well tolerated and MTD was not reached; phase II used the 5° dose level of Ch. Main grade 3-4 toxicity during all cycles: neutropenia non febrile (23/41) and 1 febrile, thrombocytopenia in 11 pts, fever in 7. At present analysis 37 pts are assessable for response: 12 (32%) partial responses (PR), 13 (35%) stable disease and 12 PD for an overall disease control rate (DCR) of 68%; median (med) duration of response was 8.2 mths. In not pre-treated there was a DCR of 78%. Major activity was observed in young pts (< 58 yrs) with a RR of 53% and interesting activity in high MSKCC risk: RR 20% and DCR 80% with a med time to progression (TTP) of 8.7 mths. Overall med TTP was 8.2 mths (CI 95% 6.9-9.4). Conclusions: This is the first study that explored the BIC tp in mRCC and it was generally well tolerated and showed promising activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
