isotretinoin and Lymphoma--T-Cell--Peripheral

We previously reported the therapeutic efficacy of 13-cis retinoic acid (13-cRA) in some subtypes of peripheral T-cell lymphoma (PTCL). This study sought to clarify if the addition of interferon-alpha2a (IFN-alpha2a), an agent with synergistic cytotoxicity with 13-cRA in many types of malignant cells, may be more effective in the treatment of PTCL. Eligible patients has histologically proven PTCL, which was recurrent after or refractory to anthracycline-containing systemic chemotherapy. The treatment included oral administration of 13-cRA 1 mg/kg/day, divided into three doses, and intramuscular injection of IFN-alpha2a 4.5 MU/M2, three times per week. From March 1995 to July 2000, a total of 17 patients, 10 men and 7 women, with a median age of 47 years (range, 18-77 years), were recruited. The histologic diagnosis included 7 cases of unspecified PTCL, 6 cases of Ki-1 anaplastic large cell lymphoma (ALCL), 1 case of angioimmunoblastic T-cell lymphoma, and 3 cases of angiocentric nasal NK/T cell lymphoma. They received a median of 1.7 months of treatment (range, 0.4-13.3 months). One patient refused further treatment due to toxicity. The doses of 13-cRA and IFN-alpha2a had to be decreased in 7 and 7 patients, respectively. Grade III/IV hematologic and non-hematologic toxicity developed in 2 and 5 patients, respectively. There were 5 partial responses (Ki-1, 4; unspecified PTCL, 1), with a total response rate of 31.3% (95% CI, 5.7-56.8%). The median duration of response for the responders was 2.5 months (range, 0.8-7.2 months). The median overall survival for the entire group of patients was 3.6 months. In conclusion, a combination of 13-cRA and IFN-alpha2a is a useful salvage treatment for selected patients with recurrent or refractory PTCL, particularly those with the Ki-1 subtype. However, the data does not support that addition of IFN-alpha2a is superior to 13-cRA alone.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Recombinant Proteins; Remission Induction; Salvage Therapy; Survival Analysis; Survival Rate

We have systemically analyzed, both in vitro and in vivo, the effect of 13-cis-retinoic acids (RA) on non-Hodgkin's lymphoma (NHL).. The in vitro growth-inhibitory effect of 13-cis-RA was examined in 11 (T cell, five; B cell, six) lymphoma cell lines by a tetrazolium colorimetric assay. A pilot clinical trial with oral 13-cis-RA 1 mg/kg/d was conducted in a selected group of 18 lymphoma patients, of whom 16 had failed to respond to at least one regimen of intensive chemotherapy. The in vitro and in vivo effects of 13-cis-RA were correlated with immunophenotypes, RA-induced changes of morphology, and patterns of DNA fragmentation of the lymphoma cells.. Four of five T-lymphoma cell lines and none of six B-lymphoma cell lines were sensitive (concentration of 50% growth inhibition [IC50] < 1.5 microns) to 13-cis-RA (P = .015). In the clinical trial, five (two Ki-1, one angioinvasive type, one diffuse mixed cell, and one diffuse large cell) complete remissions and one (Ki1) partial remission were observed in 12 patients with peripheral T-cell lymphoma (PTCL), while none of six patients with B-cell lymphoma responded to 13-cis-RA. 13-cis-RA-induced cellular differentiation and apoptosis, as evidenced by the more mature morphology, characteristic nuclear condensation, and DNA ladder pattern signifying internucleosomal fragmentation, were demonstrated in the sensitive cell lines, as well as in the remitting lymphoma tissues.. The 13-cis-RA appears to be active on lymphomas of T-lineage and their therapeutic indication may be extended to include some subtypes of PTCL. The mechanisms of action are related to differentiation and apoptosis of lymphoma cells. There appears to be no cross-resistance between 13-cis-RA and conventional chemotherapy.

Topics: Adult; Aged; Drug Screening Assays, Antitumor; Female; Humans; Isotretinoin; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Pilot Projects; Tumor Cells, Cultured