术前动脉灌注化疗结合手术治疗直肠癌疗效分析

目的 :总结和分析直肠癌术前介入灌注化疗 (Pre operativeArteraInfusionChemotherapy ,PAIC)的疗效及其优点 ,探讨直肠癌综合治疗的远期疗效。方法 :应用Seldinger方法经皮右侧股动脉穿刺 ,选择肠系膜下动脉或骼内动脉造影确定肿瘤位置后 ,注入化疗药物。术后一周进行直肠癌根治术。术后采用 5 氟尿嘧啶加甲酰四氢叶酸钙进行 6个疗程的化疗。以同期未行介入灌注治疗而手术的直肠癌患者作为对照组。结果 :PAIC组大多数患者症状、体征减轻 ,肿块缩小。介入灌注化疗前后病理检查发现肿瘤细胞有变性坏死 ,细胞核变性 ,胞浆凝固 ,间质炎细胞浸润及纤维增生等不同程度的改变。术后五年生存率 75 0 0 % ,对照组为 4 5 2 4 % ,对比差异有显著性意义 (P <0 0 5 )。结论 :术前介入灌注化疗作为直肠癌新辅助化疗方法之一是有效、安全的 ,并能提高直肠癌患者的术后长期生存时间。     

进展期结直肠癌术前经直肠5-Fu化疗的疗效观察

目的　探讨术前经直肠 5 -Fu化疗对进展期结直肠癌术后生存率的影响。方法　统计进展期结直肠癌术前经直肠 5 -Fu化疗病例 112例及对照组 14 4例 ,观察化疗反应情况并比较两组术后并发症、局部复发率、5年生存率。结果　两组术后并发症、局部复发率无显著性差异 (P >0 .0 5 ) ,但化疗组中B期病人及直肠癌病人 5年生存率均显著高于对照组 (P <0 .0 5 )。结论　进展期结直肠癌术前经直肠 5 -Fu化疗是一种有效、安全、方便的治疗措施 ,具有一定的提高生存率的作用 ,可作为术前常规应用。     

高温热疗加放射粒子植入及化疗治疗转移性盆腔肿瘤

目的观察高温热疗加放射粒子植入及化疗治疗转移性盆腔肿瘤的疗效.方法将转移性盆腔肿瘤患者分为A、B两组,A组19例,B组22例.A组给予射频加热的同时从电极处灌注2.5%的盐水以扩大肿瘤凝固性坏死的范围.不能热疗的肿瘤边缘组织内植入碘-125粒子.术后第15天开始化疗.奥沙利铂100 mg/m2,静脉滴注,第1天;CF 200 mg/m2,在5-Fu滴注前经静脉滴注2 h,继以5-Fu 200 mg/m2经静脉推注,5-Fu 400 mg/m2经静脉滴注22 h,连续5 d,3周为1周期.B组只给予化疗,化疗用药、剂量及天数与A组相同.结果第6个周期末,A组与B组的有效率分别为84.2%和36.4%,两组有效率比较差异有显著性(P＜0.01).两组的毒副反应发生率差异无显著性.结论高温热疗加放射粒子植入及化疗治疗转移性盆腔肿瘤的近期疗效好,并发症少.     

Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy.

BACKGROUND: The toxicity outcome of cancer patients receiving chemotherapy is difficult to predict. In this study the influence of malnutrition and inflammation on acute haematological toxicity was investigated. PATIENTS AND METHODS: Between January 1999 and January 2000, 48 consecutive cancer patients experienced severe haematological toxicity (SHT), either neutropenic fever or severe thrombocytopenia, following various chemotherapy regimens. Their baseline characteristics were compared with those of 59 control patients. Previous chemotherapy regimens, type of chemotherapy, performance status (PS), calculated creatinine clearance, bilirubin, C-reactive protein (1), alpha-1 acid glycoprotein (2), albumin (3), pre-albumin (4) and the nutritional and inflammatory status (NIS) ratio [NIS = (1 x 2)/(3 x 4)] were studied. Statistical analysis was carried out using either a t-test or a chi-square test. A receiver operating characteristic (ROC) curve determined the cut-off value for NIS. RESULTS: Patients experiencing SHT had a higher PS (P <0.001), inflammatory serum protein levels (P <0.001) and NIS ratio (P <0.0001), but lower haemoglobin (P <0.05) and serum-albumin levels (P <0.0001). Using a cut-off of 0 or 1 for PS and 1 for NIS, sensitivity was 98%, 43% and 89%; specificity was 38%, 90% and 66%, respectively. In 37 patients treated with topotecan as single agent, the determinants for SHT were PS (P <0.0001) and NIS (P <0.0001). CONCLUSIONS: Altered nutritional and inflammatory status correlates with increased risk of severe haematological toxicity following anticancer chemotherapy.     

Locally advanced/inflammatory breast cancers treated with intensive epirubicin-based neoadjuvant chemotherapy: are there molecular markers in the primary tumour that predict for 5-year clinical outcome?

BACKGROUND: Locally advanced and/or inflammatory breast cancer (LABC) is a heterogeneous disease. Molecular markers may help to understand this heterogeneity. This paper reports the results of a study assessing the potential prognostic or predictive value of HER-2, p53, cyclinD1, MIB1, ER and PgR expression by immunohistochemistry from patients included in an EORTC-NCIC-SAKK trial. PATIENTS AND METHODS: A total of 448 patients with a cytological or histological diagnosis of LABC were randomised into a trial comparing two anthracycline-based neoadjuvant regimens. Chemotherapy was followed by standard locoregional therapy. Survival was comparable in both arms. We collected and analysed centrally paraffin-embedded tumour specimens from 187 (72.5%) of 258 patients that had a histological diagnosis. RESULTS: Of the patients included in this molecular marker study 114 relapsed and 91 died. In the multivariate analysis p53 positivity was associated with a shorter progression-free survival [hazard ratio (HR) = 1.96; 95% CI 1.33-2.91; P = 0.0008) and a shorter overall survival (HR = 1.98; 95% CI 1.28-3.06; P = 0.002). PgR positivity predicted for a longer overall survival (HR = 0.54; 95% CI 0.35-0.83; P = 0.0045). CONCLUSIONS: p53 was an independent factor predicting for survival. In order to clarify whether p53 is a pure prognostic and/or a predictive factor, a phase III trial is being conducted (EORTC 10994/BIG 00-01 study) using functional assay in yeast from frozen tumour samples.     

Prognostic value of serial CA125 measurements during chemotherapy for patients with advanced ovarian cancer

Serum CA125 concentrations measured before and during chemotherapy may provide additional information for prognostic assessment of patients with epithelial ovarian cancer (EOC), and enable discrimination between patients who are likely to benefit from further therapy and those who will not. Medical records of 40 patients with advanced EOC, treated at the Department of Obstetrics and Gynecology of the University Hospital Nijmegen between July 1984 and April 1993, were examined. All patients had primary cytoreductive surgery followed by platinum-based chemotherapy. Serum samples were obtained before surgery and during chemotherapy. Follow-up information and patient and tumor characteristics were abstracted from medical records until December 1, 1994. By using multivariate Cox proportional hazards models for disease-free and overall survival it was evaluated whether outcome prediction was improved by inclusion of serum CA125 quantitations.
  Only FIGO stage and extent of residual tumor were significant independent prognostic factors before the start of chemotherapy. When such regression models were constructed after subsequent courses of chemotherapy, serum CA125 measurements conducted after each of the first three chemotherapy courses improved the prediction of disease-free survival. Prediction of overall survival was improved by inclusion of serum CA125 measurements after courses 1–6. Inclusion of serum CA125 measurements during chemotherapy improved prognostic assessment of patients with advanced EOC.     

Neoadjuvant cisplatin plus ifosfamide in patients with stage IIB cervical cancer: a single center phase II study

The objective of this study was to evaluate cisplatin plus ifosfamide as neoadjuvant chemotherapy with regard to toxicity and clinical response in patients with stage IIB cervical cancer. Sixty-eight patients with previously untreated stage IIB cervical cancer were given two cycles of chemotherapy: cisplatin 20 mg m⁻² on Days 1–5, infused over 1 h; ifosfamide 1.2 g m⁻² on Days 1–5 infused over 30 min. Mesna 120 mg m⁻² was administered as a bolus 15 min before ifosfamide, and a continuous infusion, delivering Mesna 1.2 g m⁻², was given subsequently over the next 16 hours. The treatment cycle was repeated on day 21. Responders were then randomized to surgery or radiation therapy. All 68 patients were evaluable for toxicity. Toxicity was found to be acceptable. One patient died at home one month after completion of the second treatment cycle. There was one grade 4 thrombocytopenia. Grade 3 toxicities included anemia in four patients, leucopenia and nausea and vomiting in one patient each. Sixty-two patients were evaluable for response. A clinical response was documented in 44 of the 55 evaluable patients (80%), with 17 complete responses (31%) and 27 partial responses (49%) (95% confidence limits 69%–91%, 19%–43%, and 36%–62% respectively). The intent-to-treat response rate was 64.7%. Twenty-one patients were randomized to surgery and 23 patients to radiation therapy. Amongst the eight patients with a complete clinical response, one patient had a complete pathological response and one patient had residual intra-epithelial neoplasia. The drug combination of cisplatin plus ifosfamide had acceptable toxicity and gave a clinical response rate of 80% in previously untreated patients with stage IIB cervical cancer.     

Extragenital malignant mixed Müllerian tumor

Reports of extragenital malignant mixed Müllerian tumor (MMMT) type though extremely rare have increased. This represents the 15th reported case of MMMT outside the female reproductive tract. A 68-year-old black woman presenting with abdominal pain, increasing abdominal girth, and a provisional diagnosis of ovarian carcinoma, underwent exploratory laparotomy, total abdominal hysterectomy, omentectomy and cytoreductive surgery. Surgery and histology revealed MMMT of heterologous type in the pelvic peritoneum, with no tumor in the genitalia and no foci of endometriosis. Despite surgical debulking leaving residual tumor of less than 1 cm followed by aggressive systemic chemotherapy, the patient died of disease within 2 months. Increasing exploratory surgery may account for the increase in reports of extragenital MMMT. Aggressive tumor debulking and multiagent systemic chemotherapy is of limited efficacy since extragenital MMMT, like uterine MMMT with pelvic spread, has short survival.     

Etoposide (VP-16) as first-line, single agentchemotherapeutic drug in low-risk gestational trophoblastic disease

Matsui H, Iitsuka Y, Seki K, Sekiya S. Etoposide (VP-16) as first-line,single agent chemotherapeutic drug in low-risk gestational trophoblasticdisease. Int J Gynecol Cancer 1997; 7: 400–404.
We reviewed the records of 73 patients with low-risk gestationaltrophoblastic disease (GTD) treated with etoposide from 1986 to 1995 at ChibaUniversity. All patients received courses of etoposide every 10 to 14 days until their human chorionicgonadotropin (hCG) concentrations had reached <1 mIU/ml or drug resistanceand/or unacceptable toxicityoccurred. Fifty-one patients (69.9%) were treated with chemotherapyalone and 22 patients (30.1%) also underwent planned hysterectomy.
Sixty-seven patients (92%) achieved a primary remission, while sixpatients (8%) required a change in drugs due to drug resistance (4patients, 5%) or toxicity (2patients, 3%). All 73 patients achieved complete remission. However, onepatient (1.4%) relapsed later.
We have demonstrated that etoposide is one of the most effective drugsagainst GTD and that the short-term toxicity is, except for alopecia,relatively mild and acceptable.Patients should, however, be informed of the possibilities of secondarymalignancies and followed-up cautiously.     

Pharmacokinetics of trofosfamide and its dechloroethylated metabolites

 To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m² Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUC_Trofo:AUC_Ifo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUC_Ifo:AUC_Cyclo 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechloroethylifosfamide in varying quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose. Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting agent for oral chemotherapy. Received 21 July 1996 / Accepted: 11 November 1996