潘生丁增强氨甲蝶呤的抗肿瘤作用

外源性核苷能抵消抗代谢药对肿瘤细胞的杀伤作用;核苷转运抑制剂潘生丁则能阻断核苷的这种抵消作用,从而增强抗代谢药的细胞毒性。本研究证明,胸苷和次黄嘌呤可明显抵消氨甲蝶呤对L1210细胞的杀伤作用,潘生丁则能有效地阻断核苷的抵消作用;潘生丁和两性霉素B合用可明显增强氨甲蝶呤对小鼠S180肉瘤的抑制作用,但不增强氨甲蝶呤对动物的毒性。提示潘生丁有可能应用于肿瘤联合化疗。     

新型双球囊导管在经皮选择性隔离肝脏灌注化疗中的应用

目的探讨自制双球囊导管在经皮选择性肝脏隔离灌注化疗(PSIHP)中的应用效果。方法实验猪12头,利用介入放射学方法进行双球囊导管选择性隔离肝脏灌注化疗结合血液灌流。化疗药物选用5-FU。比较灌注及未灌注区域肝细胞形态和凋亡指数。结果灌注区域肝细胞损伤明显,肝细胞凋亡指数(51.82%±5.34%)明显高于未灌注区域肝细胞凋亡指数(4.12%±0.84%)(P<0.01)。结论自制新型双球囊导管能有效隔离肝脏,对未灌注区域肝组织有良好的保护作用,是一种理想的隔离肝脏灌注化疗的球囊导管。     

Immediate versus delayed chemotherapy in patients with asymptomatic incurable metastatic cancer

Aim: To examine the evidence of benefit in initiating immediate chemotherapy in patients with newly diagnosed asymptomatic metastatic incurable cancer, compared with delaying chemotherapy until symptomatic progression. Methods: Through an extensive review of published reports, we examined the biological, clinical, psychological and ethical background of the issue and reported on the available clinical trial evidence in a variety of tumor types. Results: Only a limited number of clinical trials have directly examined the role of immediate versus delayed chemotherapy in patients with incurable asymptomatic metastatic cancer. Small studies in mesothelioma, colorectal cancer, breast cancer, myeloma, and low‐grade lymphoma suggest no survival benefit for the immediate initiation of chemotherapy. However, there was no evidence in other tumor types. Conclusion: The appropriate timing of chemotherapy initiation in an asymptomatic patient with metastatic cancer remains a substantial question in oncology. Many factors are likely to impact on the decision. However, little if any evidence demonstrates a clear advantage in the immediate initiation of chemotherapy in this setting.     

Progression-free interval in ovarian cancer and predictive value of an ex vivo chemoresponse assay

The study objective was to determine the effectiveness of a phenotypic chemoresponse assay in predicting response to chemotherapy measured by progression-free interval (PFI) in a retrospective series of ovarian cancer patients whose tumor specimens had been tested with the ChemoFx assay. A statistically significant correlation between assay prediction of response and PFI was observed in 256 cases with an exact or partial match between drug(s) assayed and received. In 135 cases with an exact match, the hazard ratio for progression of the resistant group was 2.9 (confidence interval [CI]: 1.4-6.3; P < 0.01) compared to the sensitive group and 1.7 (CI: 1.2-2.5) for the intermediate compared to the sensitive group. The median PFI for patients treated with drugs assayed as resistant was 9 months, 14 months for those with drugs assayed as intermediately sensitive, and PFI had not been achieved for those with drugs assayed as sensitive. These data indicate that the ChemoFx assay is predictive of PFI in ovarian cancer. As the majority of ovarian cancers display different degrees of response to different chemotherapy agents ex vivo, the incorporation of assay information into treatment selection has the potential to improve clinical outcomes in ovarian cancer patients.     

雾化吸入IL-2联合化疗对原发性非小细胞肺癌疗效观察

观察雾化吸入ＩＬ－２联合化疗对非小细胞肺癌的临床疗效并与静滴ＩＬ－２及单纯化疗进行对比。方法：ＩＬ－２的雾化１０万ｕ／次，２次／ｄ，连用１月，化疗后３ｄ开始用；ＩＬ－２静滴４０万ｕ／次，１次／ｄ，加入５００ｍｌ液体中静滴，连用１月；化疗采用动脉灌注或全身化疗，药物及剂量为环磷酰胺４００ｍｇ／ｍ２＋ＤＤＰ８０ｍｇ／ｍ２。结果：用ＩＬ－２的两组ＣＲ＋ＰＲ显著高于单纯化疗组（Ｐ＜０．０１）；雾化ＩＬ－２组ＣＲ＋ＰＲ与静滴ＩＬ－２差别无显著性（Ｐ＞０．０５），但不良反应的发生率显著低于后者，而与单纯化疗类似，结论：雾化吸入ＩＬ－２联合化疗对非小细胞肺癌有较好的疗效，且副作用小，值得扩大样本进一步验证其疗效。     

Outcome of a multicenter treatment program including autologous or allogeneic bone marrow transplantation for de novo acute myeloid leukemia

Abstract: The results of an intensive treatment program for patients 16–60 yr of age with de novo acute myeloid leukemia are presented. The patients were given conventional induction treatment with daunorubicin and cytarabine. Patients not entering complete remission (CR) after 1 course of daunorubicin/cytarabine were given 1 course of amsacrine/etoposide/cytarabine. Those entering complete remission received 3 consolidation courses using mitoxantrone, etoposide, amsacrine and cytarabine. One hundred and eighteen patients were enrolled. Complete remission was attained after 1–2 courses in 90 patients (76%). Another 6 patients reached CR after 3–4 induction courses for a total CR rate of 81%. If feasible, patients were offered either allogeneic or unpurged autologous bone marrow transplantation. Twenty-four patients underwent allogeneic bone marrow transplantation; 15 in first remission, 8 in second remission, 1 in early relapse. Thirty patients below 56 yr of age underwent autologous bone marrow transplantation in first remission. The overall probability of survival at 4 yr was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35% for the whole cohort of patients; 52% for patients below 40 yr of age. Patients undergoing allogeneic or autologous bone marrow transplantation in first remission had an overall survival of 86% and 47%, respectively, while the probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr. The CR rate and long-term results of this intensive treatment program compare favorably with other recent studies using intensive consolidation with allogeneic or autologous bone marrow transplantation or high dose cytarabine.     

Phase II study of 10-ethyl-10-deaza-aminopterin (10-EdAM; CGP 30 694) for stage IIIB or IV non-small cell lung cancer

Summary Thirty-one patients with stage IIIB or IV non-small cell lung cancer (NSCLC) were treated with intravenous 10-EdAM on a weekly basis. The starting dose was 80 mg/m², with subsequent doses adjusted depending on evidence of toxicity. There were 20 men and 11 women with a median age of 58 years (range, 33–75). Response was evaluated in 30 patients, 5 with evaluable but not measurable tumors and 25 with measurable indicator lesions. There were no complete remissions; 3 patients achieved partial remission. Nine patients had a minor response, 6 showed no change, and 12 had progressive disease. Median survival for all 31 patients was 43 weeks (range, 12–65&#x002B;). During the first 3-week period, the 10-EdAM dose was reduced or withheld in 19 patients (because of stomatitis in 12, SGPT elevation in 3, skin rash in 2, and granulocytopenia in 2), escalated in 11 patients, and unchanged in 1 patient. A mean of 34–88 mg/m²of 10-EdAM (median, 50) was given per week during the first 5-week period. Myelotoxicity was infrequent and there was no significant nephrotoxicity. Considering the modest side effects of this treatment and the conservative dose-modification schedule which mandated substantial dose reductions, we conclude that 10-EdAM is a promising antitumor agent for NSCLC.     

Prognostic Factors in Elderly Patients with Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is predominantly a disease of the elderly; the median age of incidence is 64 years, and 60% of all cases are over 60. With improved chemotherapy regimens and maximal supportive care, remission rates of up to 60% may be achieved in selected elderly patients. Whilst intensive chemotherapy is the treatment of choice for fit patients, it may be inappropriate for debilitated patients with poor prognosis disease in whom supportive care or palliative chemotherapy may be more suitable. AML in the elderly exhibits biological differences from AML in younger patients, and elderly patients may be unable to withstand the rigors of the intensive treatment regimens given to younger patients.