Meyer R M, Quirt I C, Skillings J R, Cripps M C, Bramwell V H, Weinerman B H, Gospodarowicz M K, Burns B F, Sargeant A M, Shepherd L E
Hamilton Civic Hospitals, Ont., Canada.
N Engl J Med. 1993 Dec 9;329(24):1770-6. doi: 10.1056/NEJM199312093292404.
In 1981 the Clinical Trials Group of the National Cancer Institute of Canada completed a pilot study in patients with advanced-stage non-Hodgkin's lymphoma with aggressive tumor histology. That study demonstrated the potential efficacy of escalating the dose of doxorubicin used in a regimen of bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP). In the present study, we compared standard BACOP (s-BACOP) with BACOP that included escalated doses of doxorubicin (esc-BACOP) in 238 patients 16 to 70 years old with previously untreated, advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma. During the first 28-day cycle all patients received doxorubicin in a dose of 25 mg per square meter of body-surface area on days 1 and 8. Patients randomly assigned to receive s-BACOP subsequently received five identical cycles, whereas those assigned to receive esc-BACOP received 40 mg of doxorubicin per square meter on days 1 and 8 of five subsequent cycles if granulocytopenia (< 1000 cells per cubic millimeter) had not developed during the first cycle.
The 119 patients assigned to the esc-BACOP regimen received doxorubicin at a significantly higher mean weekly dose intensity (13.5 vs. 10.4 mg per square meter per week, P < 0.001) and mean total dose (296 vs. 231 mg per square meter, P < 0.001). Because of granulocytopenia during the first cycle of therapy, only 56 of these patients (47 percent) received the escalated doses of doxorubicin. During a median follow-up of 65 months, there were no differences between the s-BACOP and esc-BACOP groups in response rate, overall survival, or survival without disease progression. When the patients who actually received the escalated doses of doxorubicin were compared with the patients in the s-BACOP group in whom neutropenia did not develop during the first treatment cycle, no difference between their outcomes was observed. Toxicity was greater in the esc-BACOP group.
In patients with advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma, escalating the dose of doxorubicin in the BACOP regimen increases toxicity but does not improve the rate of response or survival.
1981年，加拿大国立癌症研究所临床试验组对晚期侵袭性肿瘤组织学类型的非霍奇金淋巴瘤患者完成了一项试点研究。该研究证明了在博来霉素、阿霉素、环磷酰胺、长春新碱和泼尼松（BACOP）方案中增加阿霉素剂量的潜在疗效。在本研究中，我们将标准BACOP（s-BACOP）与含递增剂量阿霉素的BACOP（esc-BACOP）进行了比较，研究对象为238例年龄在16至70岁之间、先前未接受治疗的晚期中级或高级非霍奇金淋巴瘤患者。在第一个28天周期中，所有患者在第1天和第8天接受每平方米体表面积25 mg的阿霉素剂量。随机分配接受s-BACOP的患者随后接受5个相同周期的治疗，而分配接受esc-BACOP的患者，如果在第一个周期中未发生粒细胞减少（<每立方毫米1000个细胞），则在随后5个周期的第1天和第8天接受每平方米40 mg的阿霉素。
分配到esc-BACOP方案的119例患者接受阿霉素的平均每周剂量强度（13.5比10.4 mg每平方米每周，P<0.001）和平均总剂量（296比231 mg每平方米，P<0.001）显著更高。由于治疗第一个周期出现粒细胞减少，这些患者中只有56例（47%）接受了递增剂量的阿霉素。在中位随访65个月期间，s-BACOP组和esc-BACOP组在缓解率、总生存期或无疾病进展生存期方面没有差异。将实际接受递增剂量阿霉素的患者与s-BACOP组中第一个治疗周期未发生中性粒细胞减少的患者进行比较时，未观察到他们的结局有差异。esc-BACOP组的毒性更大。
在晚期中级或高级非霍奇金淋巴瘤患者中，在BACOP方案中增加阿霉素剂量会增加毒性，但不会提高缓解率或生存率。
