Procarbazine HCl is a 'nonclassical' oral alkylating anticancer agent that was first synthesized in the late 1950s. It has been used in the treatment of many cancers, but its main use is in the treatment of Hodgkin's lymphoma and brain tumors and, to a lesser extent, Non-Hodgkin's lymphoma and primary central nervous system lymphoma. Procarbazine is a prodrug that undergoes metabolic transformation into active intermediates that are thought to inhibit DNA, RNA, and protein synthesis. Early use of procarbazine in combination with mechlorethamine, vincristine, and prednisone (MOPP) was effective in the treatment of advanced Hodgkin's lymphoma, but late toxic effects such as secondary cancer and infertility led to its replacement by other regimens. However, its recent reintroduction in the dose-intensified BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen has yielded very promising findings. Procarbazine alone, or more commonly combined in the PCV (procarbazine, lomustine [CCNU], and vincristine) regimen, is also effective in treating gliomas comprising astrocytomas, glioblastomas, and oligodendrogliomas. The most common side effects of procarbazine are gastrointestinal disturbances, myelosuppression, and central nervous system effects. In conclusion, the use of procarbazine in combination with other drugs means that it remains a major anticancer drug in the management of Hodgkin's lymphoma and gliomas.
Seventy-four cases of pure acute monoblastic leukemia (AMol) have been retrospectively studied. All patients were treated at Hospital Saint- Louis between 1970 and 1978. Diagnosis was based on morphological and cytochemical features according to the FAB classification. This type of leukemia occurred at any age and in both sexes, with a high frequency of extramedullary involvements. Hyperleukocytosis was very frequent and was significantly correlated with increased blood and urine levels of lysozyme, with renal failure and hypokalemia, and with coagulation abnormalities. AMol still has a poor prognosis, despite a best remission rate (75%) obtained with rubidazone, since the duration of complete remission was short. Central nervous irradiation prolonged remission and prevented meningeal relapses, while 6 meningeal relapses occurred in the patients not irradiated. The high frequency of the extramedullary relapses, including gum and skin, emphasized the question of persistant blast cell sanctuaries after achievement of bone marrow remissions. A more intensive induction with several drugs active against monoblasts could be more efficient and prolong the duration of complete remissions.
In this study, we investigated the impact of recombinant interleukin-2 (rIL-2) after high dose chemotherapy and autologous bone marrow transplantation (ABMT) in 25 patients with refractory or relapsed Hodgkin's disease (HD) (11 patients) and non Hodgkin's lymphoma (NHL) (14 patients). 48% of patients had resistant disease, 84% achieved complete remission after ABMT. rIL-2 was started at a median of 54 days post-transplant and consisted of a first cycle of 5 days followed by 4 cycles of 2 days every other week. Patients received a mean of 160 x 10(6) IU/m2 rIL-2 and hematological toxicity was moderate and transient. None of the 5 evaluable patients with measurable disease responded to rIL-2. After a 5 year median follow-up, the probability of survival and DFS is 72% (HD: 73% and NHL: 70%, p = NS) and 45% (HD: 36% and NHL: 48%, p = NS) respectively. These somewhat encouraging results warrant further evaluation of rIL-2 after ABMT in controlled studies, especially in NHL patients stratified for previous chemosensitivity.
Objective: This multicenter phase III study compared the MEMID regimen (mitoxantrone, VP16, methylglyoxal, ifosfamide and dexamethasone) with CEOP, a CHOP-like regimen (cyclophosphamide, epirubicin, vincristine and prednisone), in elderly patients (≧65 years) with aggressive non-Hodgkin’s lymphoma (NHL). Methods: One hundred and forty-nine patients were eligible, 72 in the MEMID arm and 77 in the CEOP arm. The primary endpoint was to compare overall survival (OS) between groups, and secondary endpoints were event-free survival (EFS), response rate and toxicity. Results: Neutropenia (p < 10–5), anemia (p < 10–5) and thrombocytopenia (p = 0.0006) were significantly more frequent in patients who received MEMID. We observed an objective response rate of 55.5% in the MEMID arm and 64.9% in the CEOP arm (p = 0.24). The median OS and EFS were 15.4 and 8.5 months in the MEMID arm, and 20.3 and 10.5 months in the CEOP arm (p = 0.59 and 0.47), respectively. The median EFS was 15.4 months in the MEMID arm and 20.3 months in the CEOP arm (p = 0.59). Conclusion: The increased toxicity without survival benefit confirms the superiority of CHOP and CHOP-like regimens for elderly patient with aggressive NHL.
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