Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer

The management of rectal cancer presents substantial challenges. Patients with T3 and/or node-positive rectal cancers are at high risk for local failure and distant metastases (DM). Adjuvant radiation has been shown to decrease local recurrence (LR) rates; however, this local therapy has not been demonstrated to improve survival when compared to surgery alone. In several prospective randomized trials adjuvant chemoradiation with 5-fluorouracil-(5-FU)-based chemotherapy improved LR rates, DM rates, and overall survival (OS). The optimal chemotherapeutic regimen has not been determined; however, studies comparing standard IV bolus 5-FU administration with continuous infusion (CI) 5-FU demonstrated that CI administration was superior. Preoperative therapy has potential advantages over adjuvant therapy such as less acute bowel toxicity and improved sphincter preservation. Preoperative chemoradiation has been shown in several studies to improve LR rates and OS when compared to surgery alone. Our current approach to patients with resectable T3 or N1 cancer in the distal two-thirds of the rectum on preoperative staging is preoperative chemoradiation with planned postoperative chemotherapy. This regimen offers the best chance for local control and disease-free survival while potentially downstaging the tumor and improving sphincter preservation.     

Multidisciplinary management of metastatic colorectal cancer

When colorectal cancer metastasizes to distant organs, usually multiple sites are involved and treatment consists primarily of systemic chemotherapy and supportive care. Chemotherapeutic agents effective against metastatic colorectal cancer include 5-fluorouracil, often used in combination with leucovorin or methotrexate, and irinotecan (CPT-11). Median survival with optimal chemotherapy regimens ranges from 10 to 15 months. Less frequently, colorectal cancer metastasizes only to the liver or lung. In a minority of these cases, surgical resection can be performed and results in a median survival of 28-46 months for hepatic resections and 24-25 months for pulmonary resections. Five-year survival rates range from 24 to 38% and 21 to 44% for hepatic and pulmonary resections, respectively. For isolated liver metastases that are not surgically resectable, other regional therapies that can be considered are hepatic cryosurgery, radiofrequency ablation, and hepatic arterial infusion chemotherapy. Median survival following cryosurgery is between 26 and 30 months, while median survival following radiofrequency ablation has not been established in large series. Hepatic arterial infusion chemotherapy, especially with newer combination drug regimens, may increase survival in patients with isolated liver metastases compared to systemic chemotherapy, but this must be confirmed in randomized, prospective trials. Colorectal cancer metastases to the brain can be treated with radiation therapy or surgical resection, but median survival with treatment is less than one year.     

Growth and growth hormone in children during and after therapy for acute lymphoblastic leukaemia

Growth impairment and growth hormone (GH) deficiency have been reported in children treated for acute lymphoblastic leukaemia (ALL). We have studied growth and GH secretion in a group of 50 patients, affected by ALL, during a 2- to 5-year period after diagnosis, and in 12 long-term-survivors. We observed a significant decrease in growth velocity during the 1st year (in particular during the first 6 months) of therapy and a catch-up growth after the end of therapy. Longterm survivors did not exhibit a significant reduction of height standard deviation score (SDS), as compared to height SDS at diagnosis. None of the patients showed GH deficiency. Our data indicate that chemotherapy significantly affects growth of patients treated for ALL, whereas radiotherapy-at the doses used in this study-does not induce GH deficiency, at least not within 9 years after diagnosis.     

Chemotherapy as first treatment for primary malignant non-Hodgkin's lymphoma of the central nervous system preliminary data

Non-Hodgkin's lymphoma of the central nervous system (NHL-CNS) is thought to account for about 1 % of primary brain tumours. Radiation therapy has mainly been applied to treat cerebral lymphoma, but the low cure rate and the lack of enduring response have stimulated the search for alternatives. With the aim of postponing radiotherapy as long as possible, we tested the efficacy of a M-BACOD schedule administered immediately after histological diagnosis in 14 patients. After two M-BACOD courses 10 (71%) patients displayed an objective response (i.e. were apparently tumour-free when examined by CT). In 6 (60%) M-BACOD-responsive patients, radiotherapy was delayed for 5 months (without recurrences after a follow-up ranging from 9 to 18 months). Moreover, in 3 M-BACOD-responsive patients, no recurrence took place (even without radiotherapy) after a follow-up of 6–12 months. We conclude that radiation can be postponed after chemotherapy or delayed until tumor recurrence.This paper was presented at the 3rd Meeting of the European Neurological Society, Lausanne, 27 June–1 July, 1992     

Pharmacokinetics of sulfadiazine and trimethoprim in man

Summary Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual peak concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 µg/ml for SDZ and 0.3 to 1.1 µg/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h) – 145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 µg/ml for SDZ and from 13.8 to 93.4 µg/ml for TMP. The fraction acetylated SDZ/acetylated SDZ + SDZ was 21% during the 0–8 h period, 33% during the 8–15 h period and 41% during the 15–24 period. The average values for the notional volume of distribution, V_d, were 0.36±0.13 1/kg for SDZ and 1.39±0.25 1/kg for TMP. The average t_1/2 was 15.2±7.4 h for SDZ and 7.4±1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p<0.01) and also between the renal clearance of the two drugs (p<0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ V_d was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for acetylated SDZ. The renal clearance of acetylated SDZ averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.     

5-氟尿嘧啶对直肠癌术后骶前手术间隙灌注化疗的临床研究

目的 探索预防直肠癌术后盆内局部复发的新途径。方法 对126例直肠癌切除术后患者采用盆内能前手术间隙灌注式化疗新方法，术中盆内能前手术间隙置管，术后连续3天经该管生理盐水冲洗，术后7天灌注5—氟尿嘧啶进行盆内手术间隙化疗。结果 126例无手术死亡。术后随访5年，局部复发ll例(8．7％)，肝转移16例(12．7％)，腹膜后淋巴转移8例(6．3％)，5年生存率为74．7％。治疗副作用及术后并发症包括：白细胞减少1例，恶心呕吐5例，吻合口瘘1例，腹部伤口感染2例、会阴伤口感染3例，拖出肠段坏死1例。无盆内大出血、盆内感染等严重局部并发症。结论 所用方法操作简单，应用方便，具有高选择性区域化疗特点，全身毒副作用小，无严重局部并发症，局部复发率低，5年生存率较高，具有较好的预防局部复发效果，可望成为直肠癌切除术后防治局部复发的辅助化疗新途径。     

含羟基喜树碱联合方案治疗中晚期非小细胞肺癌

目的 :观察含羟基喜树碱 (HCPT)联合方案治疗中晚期非小细胞肺癌 (NSCLC)患者的客观疗效及毒副作用。方法 :4 6例中晚期非小细胞肺癌患者为治疗组 ,应用含羟基喜树碱方案化疗 ,其中 2 5例肺腺癌患者接受HFAP方案 ,2 1例肺鳞癌患者接受HCAP方案 ,4周为一周期 ,2周期为一疗程 ;以同期住院的未用HCPT联合化疗的同类患者 4 2例作为对照组 ,其剂量、周期、疗程与治疗组相同 ,但不用HCPT。结果 :治疗组 4 3例患者完成一疗程治疗 ,肺腺癌有效率为 5 6 % ,CR 2例 ,PR 12例 ;肺鳞癌有效率为 5 5 5 % ,CR为 0 ,PR 10例 ,总有效率 (CR +PR)为 5 5 8% ;对照组 4 2例均完成一疗程治疗 ,肺腺癌有效率为37 5 % ,CR 1例 ,PR 9例 ;肺鳞癌有效率为 33 3% ,PR 6例 ,有效率 35 7% ;两组间差异显著 (P <0 0 5 )。治疗组和对照组的毒副反应主要表现为食欲不振、脱发、恶心呕吐和白细胞及血小板减少 ,两组毒副反应发生率无显著性差异 (P >0 0 5 )。结论 :羟基喜树碱联合化疗治疗中晚期非小细胞肺癌疗效确切 ,副作用可耐受 ,该药是治疗非小细胞肺癌较为有效的药物 ,值得进一步在临床中观察和研究。     

长春瑞滨联合顺铂治疗晚期非小细胞肺癌47例疗效观察

目的：观察盖诺联合顺铂的NP方案治疗晚期NSCLC的疗效和毒性反应。方法：应用盖诺25mg／m^2静脉点滴，第1天、第8天，DDP60～80mg／m^2静脉点滴，第1天或分2天给药。结果：47例患中，无CR病例，PR25例，NC14例，PD7例，总有效率(CR PR)为53．19％(25／47)。结论：长春瑞滨联合顺铂的NP方案治疗晚期NSCLC有效率高，毒副反应可耐受。     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌

目的：研究奥沙利铂、氟尿嘧啶、亚叶酸钙联合治疗晚期大肠癌的疗效和毒性反应，并将该方案和氟尿嘧啶与亚叶酸钙联合治疗方案相比较。方法：经病理确诊的晚期大肠癌83例分为以下两组：治疗组行奥沙利铂(oxalipatin)130mg／m^2静脉滴注，第1天给药：氟尿嘧啶(5-FU)425mg／m^2静脉滴注，第1-5天给药；亚叶酸钙(CF)100mg／m^2静脉滴注，第1～5天给药；每3周重复。对照组行氟尿嘧啶(5-FU)42h5mg／m^2静脉滴注,第1～5天给药；亚叶酸钙(CF)100mg／m^2。静脉滴注，第1-5天给药；每3周重复。每例患者至少完成两个周期。结果：治疗组有效率为46．5％，常见的毒性反应为神经毒性；对照组有效率为17．5％，与治疗组差别有统计学意义，未见神经毒性，其他毒性与治疗组无统计学差异。结论：奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌,患者对其耐受良好，毒副反应较轻，疗效高于氟尿嘧啶加亚叶酸钙方案。     

L-OHP联合5-Fu和CF治疗晚期大肠癌的疗效观察

目的观察奥沙利铂联合5-氟脲嘧啶、甲酰四氢叶酸钙治疗晚期大肠癌的近期疗效。方法对43例晚期大肠癌采用奥沙利铂130mg／m^2静脉点滴2h，第1天；甲酰四氢叶酸钙200mg／m^2静脉点滴2h，第1～5天；5-氟脲嘧啶400mg／m^2静脉点滴8h以上，第1～5天。结果全组CR 1例，PR 20例，总有效率为48．8％(21／43)，中位无进展生存期为10．1个月，中位生存期为20．7个月；主要不良反应为骨髓抑制、神经毒性反应，Ⅲ度白细胞减少发生率为11．6％(5／43)，其它不良反应较轻。结论奥沙利铂联合5-氟脲嘧啶、甲酰四氢叶酸钙对晚期大肠癌有明显疗效，多数患者能耐受。