BACKGROUND: This phase I trial assessed safety, pharmacokinetics (PK), dose limiting toxicity (DLT), maximum tolerated dose and recommended dose (RD) of the combination of sorafenib plus ifosfamide in patients with advanced sarcoma. METHODS: Twelve sarcoma patients (9 soft-tissue, 3 bone sarcoma) were treated with sorafenib plus ifosfamide (starting doses 200 mg bid and 6 g/m(2) respectively). A 3 + 3 dose escalation design with cohorts of 3-6 patients was used. A study to assess the in vitro efficacy of the combination was also conducted. RESULTS: Three DLTs were observed: fatigue grade 4 with sorafenib 400 mg bid plus ifosfamide 6 g/m(2) and encephalopathy and emesis grade 3 with sorafenib 400 mg bid plus ifosfamide 7.5 g/m(2). Other toxicities included diarrhea, hand-foot syndrome, mucositis, neutropenia, skin rash and thrombocytopenia. There were no relevant effects on PK of sorafenib but an increase in ifosfamide active metabolite 4-hydroxy-ifosfamide was observed. Eight patients achieved stable disease lasting more than 12 weeks. An additive effect was observed in vitro. CONCLUSIONS: RD was sorafenib 400 mg bid plus ifosfamide 6 g/m(2), allowing administration of active doses of both agents. Limited preliminary antitumor activity was also observed. A phase II study is currently ongoing.
BACKGROUND: This phase I trial assessed safety, pharmacokinetics (PK), dose limiting toxicity (DLT), maximum tolerated dose and recommended dose (RD) of the combination of sorafenib plus ifosfamide in patients with advanced sarcoma. METHODS: Twelve sarcomapatients (9 soft-tissue, 3 bone sarcoma) were treated with sorafenib plus ifosfamide (starting doses 200 mg bid and 6 g/m(2) respectively). A 3 + 3 dose escalation design with cohorts of 3-6 patients was used. A study to assess the in vitro efficacy of the combination was also conducted. RESULTS: Three DLTs were observed: fatigue grade 4 with sorafenib 400 mg bid plus ifosfamide 6 g/m(2) and encephalopathy and emesis grade 3 with sorafenib 400 mg bid plus ifosfamide 7.5 g/m(2). Other toxicities included diarrhea, hand-foot syndrome, mucositis, neutropenia, skin rash and thrombocytopenia. There were no relevant effects on PK of sorafenib but an increase in ifosfamide active metabolite 4-hydroxy-ifosfamide was observed. Eight patients achieved stable disease lasting more than 12 weeks. An additive effect was observed in vitro. CONCLUSIONS: RD was sorafenib 400 mg bid plus ifosfamide 6 g/m(2), allowing administration of active doses of both agents. Limited preliminary antitumor activity was also observed. A phase II study is currently ongoing.
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Authors: Xavier Garcia del Muro; Antonio Lopez-Pousa; Javier Martin; Jose M Buesa; Javier Martinez-Trufero; Antonio Casado; Andres Poveda; Josefina Cruz; Isabel Bover; Joan Maurel Journal: Cancer Date: 2005-10-15 Impact factor: 6.860
Authors: David R D'Adamo; Sibyl E Anderson; Karen Albritton; Jennifer Yamada; Elyn Riedel; Kelly Scheu; Gary K Schwartz; Helen Chen; Robert G Maki Journal: J Clin Oncol Date: 2005-10-01 Impact factor: 44.544
Authors: G Grignani; E Palmerini; P Dileo; S D Asaftei; L D'Ambrosio; Y Pignochino; M Mercuri; P Picci; F Fagioli; P G Casali; S Ferrari; M Aglietta Journal: Ann Oncol Date: 2011-04-28 Impact factor: 32.976
Authors: Simon Pacey; Mark J Ratain; Keith T Flaherty; Stanley B Kaye; Lisa Cupit; Eric K Rowinsky; Chenghua Xia; Peter J O'Dwyer; I R Judson Journal: Invest New Drugs Date: 2009-12-18 Impact factor: 3.850
Authors: Robert G Maki; David R D'Adamo; Mary L Keohan; Michael Saulle; Scott M Schuetze; Samir D Undevia; Michael B Livingston; Matthew M Cooney; Martee L Hensley; Monica M Mita; Chris H Takimoto; Andrew S Kraft; Anthony D Elias; Bruce Brockstein; Nathalie E Blachère; Mark A Edgar; Lawrence H Schwartz; Li-Xuan Qin; Cristina R Antonescu; Gary K Schwartz Journal: J Clin Oncol Date: 2009-05-18 Impact factor: 44.544
Authors: Suzanne George; Priscilla Merriam; Robert G Maki; Annick D Van den Abbeele; Jeffrey T Yap; Timothy Akhurst; David C Harmon; Gauri Bhuchar; Margaret M O'Mara; David R D'Adamo; Jeffrey Morgan; Gary K Schwartz; Andrew J Wagner; James E Butrynski; George D Demetri; Mary L Keohan Journal: J Clin Oncol Date: 2009-05-18 Impact factor: 44.544
Authors: J M Buesa; A López-Pousa; J Martín; A Antón; J García del Muro; J Bellmunt; F Arranz; V Valentí; P Escudero; D Menéndez; A Casado; A Poveda Journal: Ann Oncol Date: 1998-08 Impact factor: 32.976
Authors: J M Buesa; H T Mouridsen; A T van Oosterom; J Verweij; T Wagener; W Steward; A Poveda; P M Vestlev; D Thomas; R Sylvester Journal: Ann Oncol Date: 1991-04 Impact factor: 32.976
Authors: Xavier García Del Muro; Joan Maurel; Javier Martínez Trufero; Javier Lavernia; Antonio López Pousa; Ramón de Las Peñas; Ricardo Cubedo; José Pablo Berros; Antonio Casado Herráez; Ana de Juan; Javier Martín Broto Journal: Invest New Drugs Date: 2018-03-12 Impact factor: 3.850