PMID- 19863161 OWN - NLM STAT- MEDLINE DCOM- 20100111 LR - 20131121 IS - 1532-2394 (Electronic) IS - 0898-2104 (Linking) VI - 19 IP - 4 DP - 2009 TI - A phase I clinical and pharmacokinetic study (LIPOTEC - GP PHARM/DOXO 01) of a new liposomal doxorubicin given as 3-week schedule in patients with solid tumors. PG - 261-6 LID - 10.3109/08982100902804833 [doi] AB - As a dose-finding phase I study of a new liposomal formulation of doxorubicin (LipD), patients (n = 39; median age: 60 years; range, 41-75; median ECOG performance status, 1; range, 0-2) with refractory cancer had a starting dose of LipD administered at 30 mg/m(2) as a 1-hour intravenous infusion. Cycle duration was 21 days. At the recommended dose (RD), patients received a first cycle of nonliposomal doxorubicin (non-LipD) to evaluate intrapatient pharmacokinetic differences between non-LipD and LipD. The most frequent diagnosis was head and neck tumor (7 patients). Tolerance and safety of dose levels of 30, 40, 50, 60, 70, 80, and 90 mg/m(2) were evaluated. A total of 131 cycles were administered (median per patient, 3; range, 1-6). Of the 39 patients, 8 completed the planned six cycles. Febrile neutropenia was dose limiting and defined the toxic dose of LipD as 70 mg/m(2). Other significant toxicities included asthenia (G2: 31%; G3: 8%), neutropenia (G3: 35%; G4: 29%), thrombopenia (G3: 15%; G4: 2%), anemia (G1-G2: 67%; G3-G4: 5%), mucositis (G1-G2: 32%, G3: 4%), and acute allergic reactions (G1-G2: 36%). Comparison of pharmacokinetic profiles of non-LipD and LipD showed that higher exposure was achieved with LipD. Stable disease was observed in 14 patients. We conclude that the LipD regimen, given as a 1-hour infusion every 3 weeks, is well tolerated and has a favorable pharmacokinetic profile. The recommended dose is 70 mg/m(2) with prophylactic antihistamines and corticoids to preempt allergic reaction. FAU - Majem, Margarita AU - Majem M AD - Institut Catala D 'Oncologia Duran i Reynals, L'Hospitalet de Llobregat, Spain. FAU - Salazar, Ramon AU - Salazar R FAU - Garcia, Margarita AU - Garcia M FAU - Clopes, Ana AU - Clopes A FAU - Munoz, Carme AU - Munoz C FAU - Pardo, Beatriz AU - Pardo B FAU - Martinez, Marisa AU - Martinez M FAU - Cuadra, Carmen AU - Cuadra C FAU - Montes, Ana AU - Montes A FAU - Mis, Ricard AU - Mis R FAU - Savulsky, Claudio AU - Savulsky C FAU - Ramon Germa-Lluch, Josep AU - Ramon Germa-Lluch J LA - eng PT - Clinical Trial, Phase I PT - Journal Article PL - England TA - J Liposome Res JT - Journal of liposome research JID - 9001952 RN - 0 (Antineoplastic Agents) RN - 80168379AG (Doxorubicin) SB - IM MH - Adult MH - Antineoplastic Agents/administration & dosage/adverse effects/*pharmacokinetics MH - Doxorubicin/administration & dosage/adverse effects/*pharmacokinetics MH - Female MH - Fever/chemically induced MH - Humans MH - Male MH - Middle Aged MH - Neoplasms/*drug therapy MH - Neutropenia/chemically induced EDAT- 2009/10/30 06:00 MHDA- 2010/01/12 06:00 CRDT- 2009/10/30 06:00 PHST- 2009/10/30 06:00 [entrez] PHST- 2009/10/30 06:00 [pubmed] PHST- 2010/01/12 06:00 [medline] AID - 10.3109/08982100902804833 [doi] PST - ppublish SO - J Liposome Res. 2009;19(4):261-6. doi: 10.3109/08982100902804833.