VP-16 Regimen Research Articles

Bone Marrow Transplantation for Peripheral T-Cell Lymphoma in Children and Adolescents

We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.

Enhanced Anti-Tumor Effects of Recombinant Human Tumor Necrosis Factor Plus VP-16 On Metastatic Renal Cell Carcinoma in a Xenograft Model

A nude mouse renal subcapsular and subcutaneous implantation xenograft model utilizing the SN12C human renal carcinoma cell line was investigated. In the absence of treatment, renal subcapsular implantation of SN12C resulted in metastatic spread (lung, liver and lymph nodes) and death of all animals. Radical nephrectomy of the tumor-bearing kidney after various periods of tumor implantation demonstrated that surgery alone after 18 days of tumor growth resulted in no statistically significant increase in survival with 100% of the nephrectomized animals succumbing to local recurrence and distant metastases.Recombinant human tumor necrosis factor (rTNF) and VP16 (etoposide), both well known cytotoxic and cytostatic anticancer agents, were tested singly and in combination against this metastatic model of human renal adenocarcinoma. Single agent rTNF or VP16 therapy after radical nephrectomy demonstrated only minimal efficacy with no significant decrease in local recurrence and distant metastases as compared to nephrectomy only control animals. In contrast, the combination of rTNF plus VP 16 when given after nephrectomy resulted in a significant decrease in local recurrence and no gross evidence of metastasis in any animal. Subcutaneously growing SN12C tumor nodules were also treated with the same rTNF, VP16 and combination regimens. Regression in tumor size was noted only in the combination treatment group. rTNF or VP 16, as single agents, demonstrated only slight growth inhibition that was not statistically significant.These results suggest that by combining TNF plus VP16, a synergistic enhancement of antineoplastic activity against local as well as metastatic human renal cell carcinoma can be produced.

VP-16 and cisplatin as first-line therapy for small-cell lung cancer.

Thirty-one patients with small-cell lung cancer (SCLC) were treated with VP-16 and cisplatin as first-line therapy. In the majority of cases an Adriamycin (Adria Laboratories, Columbus, Ohio) containing regimen was contraindicated because of severe cardiac or hepatic disease. Eight patients who presented with cerebral metastases were also included in the series. Eleven patients had limited disease (LD), and 20 had extensive disease (ED). Of the 28 evaluable patients, 12 (43%) achieved a complete response (CR) and 12 (43%) had a partial response (PR). Four patients (14%) either had no response or progressed on treatment. The median duration of response for patients with LD was 39 weeks and for those with ED, 26 weeks. The median survival time (MST) for the whole group of responding (CR and PR) LD patients was 70 weeks (range, 28 to 181 + weeks), and for responding ED patients, it was 43 weeks (range, 17 to 68 weeks). Gastrointestinal toxicity was mild, but leukopenia and thrombocytopenia were common. There were four febrile episodes during periods of drug-induced neutropenia and this led to one treatment-related death. Nephrotoxicity occurred in 15 patients and required discontinuation of cisplatin in two. These results compare favorably with reports of standard induction chemotherapy regimens and provide further evidence of the activity of the VP-16 and cisplatin regimen in patients with SCLC.

Vinblastine, Actinomycin D, Bleomycin, Cyclophosphamide and Cis-Platinum for Advanced Germ Cell Testis Tumors: Brazilian Experience

Disseminated germ cell testicular cancer proved to be highly sensitive to platinum-containing chemotherapy regimens. We present data concerning the treatment of advanced seminoma and nonseminomatous tumors in a developing country. We treated 30 patients with advanced germ cell testis tumors with 3 or 4 cycles of vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum. Surgical resection of residual masses was done 30 days after completion of chemotherapy in 18 patients. The histology of the primary tumor was seminoma in 13 patients and nonseminomatous tumors in 17. Toxicity was mild and no treatment-related deaths occurred. All 13 patients (100 per cent) with seminoma and 12 of 17 patients (71 per cent) with nonseminomatous tumors had a complete response to chemotherapy, and 1 of 17 patients was free of disease after a debulking operation and additional chemotherapy. A total of 3 patients with seminoma and 2 with nonseminomatous tumors had recurrences 5 to 8 months after an initial complete response and received additional chemotherapy (VP-16 regimen) with or without radiotherapy. Complete clinical response was achieved in 4 of 5 patients. Median followup was 24 months (range 8 to 38 months) in the 13 patients with seminoma and 28 months (range 9 to 58 months) in those with nonseminomatous tumors, and 13 (100 per cent) and 12 (71 per cent), respectively, are alive without evidence of disease. These data suggest that the protocol of vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum is highly effective and minimally toxic in the treatment of disseminated germ cell testicular cancer, inducing an 83 per cent long-lasting clinical remission. Seminomas seem to be equally or even more sensitive than nonseminomatous tumors to this platinum-containing chemotherapy regimen. Recurrence after initial complete response can be treated successfully with regimens containing VP-16.