pentostatin and Carcinoma--Renal-Cell

Topics: Carcinoma, Renal Cell; Cyclosporine; Graft Survival; Graft vs Host Disease; Humans; Leukocyte Transfusion; Pentostatin; Peripheral Blood Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Homologous

The National Cancer Institute of Canada Clinical Trials Group undertook a phase II study of 2'-deoxycoformycin in patients with metastatic renal cell carcinoma. When 2'-deoxycoformycin 4 mg/m2 was administered intravenously weekly for three weeks then every two weeks no significant antitumor activity was noted in 19 evaluable patients. Toxic effects experienced were as expected, consisting primarily of nausea/vomiting, anorexia, and lethargy. It is concluded that 2'-deoxycoformycin at this dose and schedule has no clinical activity in the treatment of metastatic renal cell carcinoma.

Topics: Adult; Aged; Carcinoma, Renal Cell; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Pentostatin

We hypothesized that lymphoid-selective host conditioning and subsequent adoptive transfer of sirolimus-resistant allogeneic T cells (T-Rapa), when combined with high-dose sirolimus drug therapy in vivo, would safely achieve antitumor effects while avoiding GVHD.. Patients (n = 10) with metastatic renal cell carcinoma (RCC) were accrued because this disease is relatively refractory to high-dose conditioning yet may respond to high-dose sirolimus. A 21-day outpatient regimen of weekly pentostatin (P; 4 mg/m(2)/dose) combined with daily, dose-adjusted cyclophosphamide (C; ≤200 mg/d) was designed to deplete and suppress host T cells. After PC conditioning, patients received matched sibling, T-cell-replete peripheral blood stem cell allografts, and high-dose sirolimus (serum trough target, 20-30 ng/mL). To augment graft-versus-tumor (GVT) effects, multiple T-Rapa donor lymphocyte infusions (DLI) were administered (days 0, 14, and 45 posttransplant), and sirolimus was discontinued early (day 60 posttransplant).. PC conditioning depleted host T cells without neutropenia or infection and facilitated donor engraftment (10 of 10 cases). High-dose sirolimus therapy inhibited multiple T-Rapa DLI, as evidenced by stable mixed donor/host chimerism. No antitumor responses were detected by RECIST criteria and no significant classical acute GVHD was observed.. Immune-selective PC conditioning represents a new approach to safely achieve alloengraftment without neutropenia. However, allogeneic T cells generated ex vivo in sirolimus are not resistant to the tolerance-inducing effects of in vivo sirolimus drug therapy, thereby cautioning against use of this intervention in patients with refractory cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Cyclophosphamide; Female; Graft vs Tumor Effect; Humans; Immunophenotyping; Immunotherapy, Adoptive; Lymphocyte Depletion; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Pentostatin; Peripheral Blood Stem Cell Transplantation; Phenotype; Sirolimus; T-Lymphocyte Subsets; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome

Topics: Adult; Aged; Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Pentostatin; Pilot Projects