Gobbi P G, Pieresca C, Federico M, Di Renzo N, Narni F, Iannitto E, Grignani G, Cavanna L, Avanzini P, Partesotti G
Università di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) S. Matteo, Italy.
J Clin Oncol. 1993 Apr;11(4):712-9. doi: 10.1200/JCO.1993.11.4.712.
We explored the feasibility, toxicity, and preliminary results of a chemotherapy (CT) regimen, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and vinblastine (EBV)/lomustine (CCNU), doxorubicin, and vindesine (CAD), derived through hybridization, shortening, and intensification of a corresponding 10-drug alternating combination CAD/MOPP/doxorubicin, bleomycin, and vinblastine (ABV), effective in treatment of advanced Hodgkin's disease (HD).
Hybridization involved all drugs except CCNU and mechlorethamine, which were administered in alternating cycles; the length of therapy was reduced from nine to six cycles. The average projected drug doses during the six cycles were increased by 42%, with an overall 1.54 dose-intensification; epidoxorubicin was substituted for doxorubicin at equivalent tumoricidal doses. Radiotherapy (RT) was optional and its indications were limited.
Eighty assessable patients with previously untreated, advanced or unfavorably presenting HD were treated in nine cooperating institutions between 1988 and 1991. RT was delivered to 22 patients. Remissions were complete (CR) in 75 patients (93%), partial in three (4%), and null in two (3%). The median relative dose-intensity was 0.71 for the overall regimen. Three of five patients who failed to achieve CR, and two of the four who relapsed, received lower relative dose-intensive cycles. Nonhematologic toxicity was acceptable, but there was considerable hematologic toxicity. Fatal gastrointestinal bleeding was seen in one patient.
Caution is advised due to the short median follow-up period. Nevertheless, in addition to the excellent response rate, (1) the results were reached through abbreviation, intensification, and hybridization of an existing alternating regimen; (2) RT had limited use in this program, which may have contributed to lowering the risk of second tumors; and (3) the results were obtained in a multicenter study (a condition that often impairs results from clinical trials).
我们探讨了一种化疗（CT）方案的可行性、毒性及初步结果，该方案是通过对相应的10药交替联合方案环磷酰胺、阿霉素、长春地辛（CAD）/氮芥、长春新碱、丙卡巴肼、泼尼松（MOPP）/表柔比星、博来霉素、长春花碱（EBV）进行杂交、缩短及强化而得来的，该10药交替联合方案对晚期霍奇金病（HD）治疗有效。
杂交涉及除洛莫司汀（CCNU）和氮芥之外的所有药物，这两种药物采用交替周期给药；治疗疗程从9个周期减至6个周期。6个周期内预计的平均药物剂量增加了42%，总体剂量强度为1.54；表柔比星在等效杀肿瘤剂量下替代了阿霉素。放射治疗（RT）为可选方案，其适应证有限。
1988年至1991年间，9家合作机构对80例先前未治疗的、晚期或表现不佳的可评估HD患者进行了治疗。22例患者接受了RT。75例患者完全缓解（CR）（93%），3例部分缓解（4%），2例无缓解（3%）。整个方案的中位相对剂量强度为0.71。5例未达到CR的患者中有3例，4例复发患者中有2例接受了较低相对剂量强度的周期治疗。非血液学毒性可以接受，但血液学毒性较大。1例患者出现致命性胃肠道出血。
鉴于中位随访期较短，建议谨慎对待。然而，除了出色的缓解率外，（1）这些结果是通过对现有交替方案进行缩短、强化和杂交获得的；（2）RT在本方案中的应用有限，这可能有助于降低二次肿瘤的风险；（3）这些结果是在一项多中心研究中获得的（多中心研究往往会影响临床试验结果）。
