ABSTRACT
An international, Phase II trial was conducted to assess two doses of ofatumumab, a human CD20 monoclonal antibody, combined with cyclophosphamide (750 mg/m(2) ), doxorubicin (50 mg/m(2) ), prednisone (100 mg days 3-7) and vincristine (1·4 mg/m(2) ) (O-CHOP), as frontline treatment for follicular lymphoma (FL). 59 patients with previously untreated FL were randomized to ofatumumab 500 mg (n = 29) or 1000 mg (n = 30) day 1, with CHOP on day 3 every 3 weeks for six cycles. Median duration of FL was 0·1 years for both dose groups; 34% and 38% of patients had high-risk Follicular Lymphoma International Prognostic Index (FLIPI) scores in the 500- and 1000-mg dose groups, respectively. Overall response rate was 90% for the 500-mg group and 100% for the 1000-mg group. 62% of patients achieved complete response (CR)/unconfirmed CR (CRu). 76% of patients with FLIPI score 3-5 attained CR/CRu. Longer follow-up time is needed for analysis of survival end points. The most common Common Terminology Criteria grade 3-4 investigator-reported adverse events were leucopenia (29%) and neutropenia (22%). No deaths have been reported. O-CHOP was safe and efficacious in patients with previously untreated FL, including high-risk FLIPI groups. This trial was registered at www.clinicaltrials.gov (NCT00494780).
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Lymphoma, Follicular/diagnostic imaging , Male , Middle Aged , Positron-Emission Tomography , Prednisone/administration & dosage , Treatment Outcome , Vincristine/administration & dosageABSTRACT
Oral administration of Lu 35-138, a low aqueous soluble compound, was investigated in three different formulations containing sulfobutylether ß-cyclodextrin (SBE7ßCD) in fasted beagle dogs. The evaluated formulations was (i) a SBE7ßCD solution, (ii) a spray dried solution filled into hard gelatine capsules, and (iii) a direct compressible tablet containing SBE7ßCD. The three formulations did not lead any significant differences in the obtained AUCs, though a trend was observed for the highest absorption when Lu 35-138 was dosed in the cyclodextrin solution. These results demonstrate that a solid formulation with a relative low content of cyclodextrins can be used to increase the bioavailability of a low water soluble compound to a relative high level when compared to a cyclodextrin solution.