Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.

BACKGROUND: Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma. MATERIAL AND METHODS: Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity. RESULTS: There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences.Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis. CONCLUSION: Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.     

Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion.

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone.     

A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro-Oncologia

BACKGROUND: No data on the role of chemotherapy in recurrent ependymal tumors are available in adults. The aim of the current study was to investigate outcomes after salvage chemotherapy in this setting. METHODS: A retrospective review was made of the charts of 28 adults (> or = 18 years) with progressive or recurrent ependymal tumors after surgery and radiotherapy, who received chemotherapy between 1993 and 2003 in 3 institutions of the Gruppo Italiano Cooperativo di Neuro-Oncologia network. RESULTS: Thirteen patients (46.3%) received cisplatin-based chemotherapy (Group A) and 15 (53.7%) received regimens without cisplatin (Group B). Platinum-based chemotherapy yielded 2 complete responses (CR) (15.4%) and 2 (15.4%) partial responses (PR), whereas 7 patients (53.8%) remained stable (SD). After regimens without cisplatin, there were no CR, 2 PR (13.3%), and 11 SD (73.3%). The overall median time to progression was 9.9 months (95% confidence interval [95% CI], 7.5-21.7 months), 9.9 months (5.2-not reached) for Group A and 10.9 months (95% CI, 7.17-23.9 months) for Group B. The overall median survival (OS) was 40.7 months (95% CI, 16-not reached), 31 months (21-not reached) for Group A and 40.7 months (13.4-not reached) for Group B. CONCLUSIONS: Cisplatin-based chemotherapy achieved a higher response rate, but did not prolong disease progression-free survival or OS. More active regimens for the salvage treatment of ependymal tumors have yet to be found.     

改进的多西紫杉醇联合顺铂方案治疗晚期非小细胞肺癌的临床观察

目的目前临床上广泛应用多西紫杉醇联合顺铂作为晚期非小细胞肺癌（NSCLC）的一线化疗方案，但传统3wk方案毒副反应较大。因此本研究为比较多西紫杉醇联合顺铂改进的3wk方案与传统3wk方案治疗晚期NSCLC的疗效、毒副反应及1a生存率。方法68例经组织学或细胞学确诊的Ⅲb或Ⅳ期NSCLC病人，随机分为两组，分别接受改进方案（A组）和传统3wk方案（B组）化疗。A组：多西紫杉醇总剂量按75mg／m^2，分2次分别于d1、d8，静脉滴注；每天顺铂25mg／m^2，静脉滴注，dl-d3，每3wk重复；B组：多西紫杉醇75mg／m^2，静脉滴注，d1，顺铂用法同A组，每3wk重复。2周期后评价疗效与毒副反应，并随访la生存率。结果两组均无CR，A组PR10例，SD20例，PD4例，总有效率为29.4％；B组PR11例，SD20例，PD3例，总有效率为32.4％；A组1a生存率为38．2％，B组1a生存率为35.3％，两组疗效（P=0．793）及1a生存率（P=0．801）差异无显著性。中性粒细胞Ⅲ／Ⅳ度减少A组17．6％；B组47．1％，两组差异有显著性（P=0．010）。结论多西紫杉醇联合顺铂改进的3wk方案治疗NSCLC与传统3wk方案相比，疗效相似，但血液学毒性明显下降，耐受性好。     

Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients

Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunohistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in > or = 50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in > 50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.     

Comparison of antiemetic activity of chloropromazine and high doses of metoclopramide in cisplatin-based chemotherapy

High dose metoclopramide and different phenothiazines are widely used antiemetics in cancer patients receiving chemotherapy. In a prospective randomized study we compared the antiemetic efficacy of high dose metoclopramide (M) and chloropromazine (C). We also tested the role of dexamethasone (D) when combined with either of these drugs. A total of 165 patients were randomly allocated to 5 groups with 33 patients in each group. Group A received only M, group B: M + D, group C: C + D, group D: M + D + C and group E: M + C. All patients received combination chemotherapy with cisplatin for the first time and were evaluated only once in order to exclude anticipatory nausea and vomiting. Patients in group C had less antiemetic protection than the other groups (p less than 0.001). Groups A, B, D, E, had more or less equal antiemetic efficacy, although the efficacy in group B was somewhat better; this difference was not statistically significant. Side-effects were minimal. Chloropromazine seemed to protect patients who received metoclopramide from extrapyramidal manifestations. In conclusion the results suggest that high dose metoclopramide has a better antiemetic effect than chloropromazine, dexamethasone is a helpful adjuvant drug when used in combination with an effective antiemetic agent, and chloropromazine and dexamethasone may prevent the extrapyramidal side-effects that can occur when metoclopramide is used as single antiemetic drug.     

PFC方案化疗联合高强度聚焦超声治疗进展期胃癌的临床观察

目的:评价PFC方案化疗联合高强度聚焦超声(HIFU)治疗进展期胃癌的疗效和不良反应。方法:经病理学确诊的进展期胃癌患者60例,分A、B两组,每组30例。A组予PFC方案(紫杉醇+氟尿嘧啶+顺铂)化疗的同时行病灶部位HIFU治疗;B组单用PFC方案化疗。结果:60例均可评价疗效,A组CR5例(16.7%),PR17例(56.7%),SD4例(13.3%),PD4例(13.3%),有效率(CR+PR)73.3%,中位生存期13.9月;B组CR2例(6.7%),PR14例(46.7%),SD7例(23.3%),PD7例(23.3%),有效率53.3%,中位生存期9.6月。二组有效率无显著性差异(P>0.05),中位生存期差异有显著性(P<0.05)。主要不良反应为骨髓抑制、恶心、呕吐和脱发,二组无显著性差异(P>0.05)。结论:PFC方案化疗结合HIFU治疗进展期胃癌为一种新的疗法,其近期疗效确切,不良反应轻,患者能耐受,且能明显改善患者的中位生存期,延长患者生命,对于进展期胃癌患者如能在化疗的同时联合HIFU治疗则不失为有效治疗手段,值得深入探讨。     

Aberrant p53 staining does not predict cisplatin resistance in locally advanced non-small cell lung cancer

Cisplatin based chemotherapies have increased the survival in nonsmall cell lung cancer. A mechanism for identifying tumors resistant to cisplatin would be useful in avoiding unnecessary toxicity of platinum regimens. Mutation of p53 has been shown to induce chemotherapy resistance in vitro. We hypothesized that tumors staining for p53 would be resistant to cisplatin. In Cancer and Leukemia Group B protocol 8935, patients with stage IIIA (N2 node positive) nonsmall cell lung cancer received chemotherapy followed by surgery, then post-operative chemotherapy and/or radiation. All patients underwent pre-treatment staging mediastinoscopy. Twenty-five out of forty-nine pre-treatment mediastinal lymph node specimens stained positively for p53. Positive staining did not correlate with response to chemotherapy or survival. It did predict a slightly higher complete or partial resection rate compared to negative staining (76 vs. 45%) (p = 0.042). A trend toward longer median survivals was seen in patients with positive p53 staining. This study does not support the ability of p53 staining to predict chemotherapy resistance.     

Induction chemotherapy with carboplatin and ftorafur in advanced head and neck cancer. A randomized study.

From 1987 to 1989, 42 patients with locally advanced squamous cell carcinoma of the head and neck (Stages III-IV, Mo) were randomized to receive radiotherapy (Group A) or three courses of induction chemotherapy followed by radiotherapy (Group B). There were 36 evaluable patients, 17 in Group A and 19 in Group B. The radiotherapy regimen was the same for both groups, 66-74 Gy total tumor doses with standard fractionation scheme of 2 Gy/day. The chemotherapy regimen was a combination of carboplatin 400 mg/m2 by intravenous bolus injection on day 1, and Ftorafur 1,000 mg/m2 orally once a day for 14 days. Cycles were given every 4 weeks. The complete response rate in Group A was 65%; in group B it was 31.5% after induction chemotherapy and 84% after radiotherapy. The 42-month actuarial overall survival rates were 34% for Group A and 47% for Group B (P = NS). Patients from both groups with a complete response had a significantly longer survival time than those with a partial response (P less than 0.001). No significant differences in disease-free survival were found between the two treated groups. The chemotherapy regimen was well tolerated, with moderate hematologic and gastrointestinal toxicity. Increased in radiation toxicity by chemotherapy was not observed.     

Chemotherapy for gastric cancer that recurs after adjuvant chemotherapy with S-1

We retrospectively analyzed the efficacy of chemotherapy in patients whose gastric cancer recurred after adjuvant chemotherapy with S-1. A total of 51 patients were evaluated. Twenty-one patients received S-1-containing chemotherapy as first-line treatment after recurrence [cohort A: S-1 plus cisplatin (n = 10), S-1 monotherapy (n = 7), S-1 plus irinotecan (n = 3) and S-1 plus docetaxel (n = 1)]. The other 30 patients received a non-S-1-containing regimen [cohort B: paclitaxel or docetaxel (n = 22), irinotecan plus cisplatin (n = 6) and other drugs (n = 2)]. No objective responses occurred in cohort A, while five patients achieved a partial response in cohort B (response rate, 0 versus 16%; P = 0.04). Median progression-free survival was significantly longer in cohort B than in cohort A (4.3 versus 2.3 months, P = 0.02). S-1-containing chemotherapy does not appear to be effective in patients whose gastric cancer recurs after adjuvant S-1 chemotherapy. Other chemotherapeutic agents should be evaluated in this setting.     

异长春花碱加顺铂联合放射治疗晚期非小细胞肺癌

目的 :观察以异长春花碱加顺铂方案化疗联合胸部放疗综合治疗不可切除的晚期非小细胞肺癌的临床疗效及毒副作用。方法 :31例晚期非小细胞肺癌患者接受异长春花碱加顺铂方案化疗联合胸部放疗 (放化疗组 ) ,与同期单纯接受化疗的 32例 (化疗组 )对比。结果 :近期客观有效率 ,中位生存期和 1年、2年、3年生存率 :放化疗组分别为 5 1 6 % ,13个月和5 2 8%、2 8 8%、17 2 % ;而化疗组则为 4 6 9% ,12个月和 4 5 6 %、19 8%、7 1% ,两组无显著差别 (P >0 0 5 )。但近期有效者 ,放化疗组的中位生存期为 17个月 ,而化疗组则为 12个月 ,放化疗组显著高于化疗组 (P <0 0 5 )。毒副作用可耐受 ,无治疗相关性死亡。结论 :以异长春花碱加顺铂方案化疗联合胸部放疗治疗不可切除的晚期非小细胞肺癌有效安全。与同期单纯接受化疗的对照组相比 ,两组疗效无显著差异 ,但近期有效者例外。     

Follow-up study of preoperative oral administration of an antineoplastic agent as an adjuvant chemotherapy in stomach cancer

Based on the propensity of fat emulsion to be absorbed mainly into lymphatic capillaries and regional lymph nodes, preoperative oral administration of 5-FU emulsion was attempted as an adjuvant chemotherapy to surgery for gastric carcinoma. In our previous studies, it was demonstrated that the mean 5-FU level in the regional lymph nodes was higher in patients who received the 5-FU solution. Since 1974, we have administered 5-FU emulsion preoperatively to 167 patients with gastric cancer (500 mg X 10 days) and examined histologically the effect of this regimen on the metastatic foci in the lymph nodes. A positive change, such as marked necrosis or marked degeneration, was found in 58% of the metastatic lesions. Sixty-four patients with advanced cancer who received the preoperative 5-FU emulsion also received a curative resection between 1974 to 1977 in addition to postoperative chemotherapy (MMC 40 mg and 5-FU more than 5000 mg) (Group A). Their survival rate was compared with that of the curatively operated advanced cancer patients from 1959 to 1973 who received the same postoperative chemotherapy only (Group B, N = 59) and with that of patients, from 1959 to 1970, who received no chemotherapy (Group C, N = 222). The 5 year survival rate of Group A was 0.53 +/- 0.07, which was higher than that (0.49 +/- 0.07) of Group B and that (0.40 +/- 0.10) of Group C. Comparing the 5-year survival rates of the 3 groups from several points of view, such as a stage of cancer progress absence of serosal invasion, the 5-year survival rate of group A was higher than that of other groups. Although these differences between Group A and B were not statistically significant, but those between Group A and B were significant. From these results it is suggested that preoperative oral 5-FU emulsion might be effective as an adjunct to surgery for gastric cancer.     

适形调强放疗联合化疗治疗中晚期非小细胞肺癌72例

目的:评价三维适形调强放疗联合化疗在治疗中、晚期非小细胞肺癌(NSCLC)的作用。方法:72例中、晚期NSCLC患者采用分组治疗。A组采用常规放疗加化疗,共30例;B组采用三维适形放疗加化疗,共30例;C组采用三维适形调强放疗加化疗,共12例。三组均采用铂类联合盖诺方案化疗1个周期后放疗,放疗结束后再化疗3~5个周期。结果:A组有效率(CR PR)43·3%,B组有效率70%·0,C组有效率83·3%,A组与B组,A组与C组差异有统计学意义,P<0·05;1年生存率:A组40·0%(8/20),B组为66·7%(12/18),C组为100·0%(4/4)。B、C组合并后的1年生存率与A组差异有统计学意义,P=0·03;三组的骨髓抑制等基本相同;放射性食管炎,三组间差异无统计学意义,P=0·16。急性放射性肺炎:A组56·7%,B组33·3%;C组16·7%。A组与C组差异有统计学意义,P=0·031。结论:在中、晚期NSCLC的治疗中,三维适形或调强放疗联合化疗与与常规放疗联合化疗相比,具有疗效好、毒副反应轻、患者容易耐受等特点;适形调强放疗在不增加放疗不良反应的同时,能够提高1年生存率和靶区的照射剂量。     

Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin

In a series of three consecutive pilot studies carried out between 1977 and 1981 at Wayne State University, Detroit, Michigan, designed to test the feasibility of multimodality therapy in patients with previously untreated advanced squamous cell carcinoma of the head and neck, patients received three different induction chemotherapy regimens: cisplatin + Oncovin (vincristine) + bleomycin (COB) for two courses; 96-hour 5-fluorouracil (5-FU) infusion and cisplatin for two courses, or 120-hour 5-FU infusion + cisplatin for three courses. Over-all response rates (complete response + partial response) to each of the three induction chemotherapy regimens were high: 80%, 88%, and 93%, respectively. Superior complete response rate in the group receiving three courses of 120-hour 5-FU infusion + cisplatin was 54% versus 29% for COB and 19% for two-course 96-hour 5-FU infusion + cisplatin (P = 0.04). Significant survival advantage at 18 months minimum follow-up for the group receiving three courses of 120-hour 5-FU + cisplatin induction therapy was found. Actual T and N stage may influence the clinical complete response rate. Responders to initial chemotherapy have significantly better survival as compared to nonresponders regardless of subsequent surgery and/or radiotherapy. These studies show that a multimodality approach to management of advanced head and neck cancer is feasible. Superior complete response rate and survival in one of the treatment groups suggest that choice of induction chemotherapy regimens and/or number of courses is of prime importance in such multimodality treatment programs.     

Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer

Cisplatin-based chemotherapy is being tried in the treatment of nonoperable cases of non-small-cell lung cancer (NSCLC). However, the prognosis is unfavorable and to improve survival, clinical studies using various combinations of a variety of drugs as well as experimental material are in progress. We compared the efficacy and toxicities of combination chemotherapy using different doses of vinorelbine and ifosfamide with a constant dose of cisplatin in this study. Patients diagnosed with inoperable stage III or IV NSCLC between June 1997 and December 1998 were included. Cisplatin was administered at a constant dose of 80 mg/m2 on day 5, whereas vinorelbine on days 1 and 5 and ifosfamide on day 5 were administered in one of two different doses. In arm A, vinorelbine 25 mg/m2 and ifosfamide 3.0 g/m2 were administered. In arm B, vinorelbine 20 mg/m2 and ifosfamide 2.5 g/m2 were administered. Also, we reviewed for phase II and III studies that test 1) cisplatin, 2) vinorelbine monotherapy, and 3) vinorelbine/cisplatin/ifosfamide combination chemotherapy for stage IIIb-IV non-SCLC. Summation dose intensity (SDI) was calculated in each published and current study. Twenty patients in arm A and 35 patients in arm B were available for evaluation. There was no difference in patient activity, pathologic diagnosis, and differentiation or stage between the two arms. The median number of cycles was four in both arms. The response rate was 50% in arm A and 30% in arm B. The median survival times for arm A and B were 40 and 42 weeks, respectively, whereas the SDI was 1.94 and 1.7, respectively. More than grade III leukopenia was observed in 28.9% in arm A, which is more frequent than the 17.2% in arm B. There was a significant correlation between the SDIs and response rates and median survival (r2 = 0.629, p = 0.001; r2 = 0.453, p = 0.001, respectively). Although the follow-up period is relatively short, the survival time was similar in both arms. Because a high response rate may not be followed by a high survival time in combination chemotherapy of NSCLC, further studies on the appropriate dose of individual agents with regard to the relationship between response rate, severity, and incidence of toxicities and survival rate should be carried out.     

A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer

Purpose

To assess the therapeutic value of biomarker-guided chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Eighty-five NSCLC patients at stage IIIb or IV were divided into two groups based on the feasibility of biomarker analysis. Group A included patients with biomarker data (n = 41); Group B were patients without biomarker results (n = 44). Tumor samples obtained by fiberoptic bronchoscopy and computerized tomography-guided needle biopsy were analyzed by immunohistochemistry for intratumoral level of excision repair cross-complementing gene 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and β-tubulin III. Chemotherapy regimens in Group A were determined according to the status of molecular signatures, whereas a standard gemcitabine plus cisplatin regimen was used for Group B. Tumor response, patient survival, and adverse effects were monitored for both groups.

Results

The overall response rate, defined as complete response plus partial response, was 56.1 % for Group A, significantly higher than that in Group B (31.8 %; P = 0.024). The median progression-free survival (PFS) time was 5.2 months for Group A, significantly longer than that of Group B (4.1 months; P = 0.026). The 1-year survival rate of Group A was 65.9 %, significantly higher than that of Group B (40.9 %; P = 0.021), whereas the median overall survival times were 13.5 versus 12.5 months for Groups A and B, respectively (P = 0.483). The adverse effects in the two groups were essentially the same.

Conclusions

Biomarker-tailored chemotherapy based on ERCC1, RRM1, and β-tubulin III expression showed significantly increased response rate, median PFS time, and 1-year survival rate in patients with NSCLC.     

Adjuvant chemotherapy after curative resection for gastric cancer-5'-DFUR + cisplatin vs 5'-DFUR

A prospective randomized study involving gastric cancer patients was conducted to evaluate combined adjuvant chemotherapy. Forty-two patients under 80 years of age who underwent a curative resection of pathologic stage II or III gastric cancer were randomly assigned to receive adjuvant chemotherapy containing the following two regimens from 1993 to 1996. A) Oral 5'-deoxy-5-fluorouridin (5'-DFUR) plus cisplatin: 5'-DFUR, daily administration, combined with CDDP 15 mg/m2/day, 30-min drip infusion, fortnightly for 8 weeks, repeated every 16 weeks. B) Oral 5'-DFUR alone: 5'-DFUR, daily administration. The dosages of 5'-DFUR were assigned according to the patients' body surface area (BSA): BSA < 1.7 m2, 600 mg and BSA > or = 1.7 m2, 800 mg, daily administration, bid. Twenty patients were assigned to regimen A, and 22 to regimen B. All clinicopathological factors were equally distributed in each regimen. No adverse reactions greater than grade 3 occurred in either regimen. There was no significant difference between the two regimens in overall survival or overall disease-free survival. For patients with positive nodes, the 5-year disease-free survival rates were 56.4% in A and 38.3% in B (p = 0.29). In stage III patients, the 5-year disease-free survival rates were 55.6% in A and 20.7% in B (p = 0.26). No significant survival benefit was observed with the combined chemotherapeutic regimen, 5'-DFUR plus cisplatin, compared with 5'-DFUR alone.     

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.     

Loss of hMLH1 expression correlates with improved survival in stage III-IV ovarian cancer patients

Pre-clinical data suggest a relationship between DNA MisMatch Repair (MMR) system failure, particularly the inactivation of genes hMLH1 and hMSH2, and resistance to drugs like cisplatin and carboplatin. We studied the correlation between loss of hMLH1 expression in tumour cells and clinical outcome in 38 patients with ovarian cancer, who underwent cisplatin-based chemotherapy. 19 patients (56%) showed loss of hMLH1 expression (Group A) while 15 patients (44%) showed normal hMLH1 expression (Group B). 4 patients were not evaluable for hMLH1 expression. The 2 groups of patients were similar for clinical characteristics, response to chemotherapy and time to progression. Group A patients showed a median survival of 55 months whereas Group B patients had a median survival of 12 months (P=0.014). Loss of hMLH1 expression was the only independent predictor of survival in the multivariate analysis. Our observations suggest a relationship between loss of hMLH1 and improved survival in advanced ovarian cancer.     

The role of metoclopramide in acute and delayed chemotherapy induced emesis: a randomised double blind trial

High dose metoclopramide is an effective anti-emetic for use with cisplatin containing chemotherapy regimens but can cause extrapyramidal reactions. Lorazepam and dexamethasone are increasingly being used to alleviate chemotherapy induced emesis. This trial has assessed the contribution of high dose metoclopramide to anti-emetic control when given with dexamethasone and lorazepam. Eight-one patients receiving chemotherapy, mainly for gynaecological malignancy, entered a randomised double blind cross-over trial comparing dexamethasone and lorazepam with or without a 24 h metoclopramide infusion. This was followed by oral dexamethasone with or without oral metoclopramide for three further days depending on the initial randomisation. Sixty-one patients were fully evaluable. Fifty-five received cisplatin containing regimens and six non-cisplatin regimens. There was a significant reduction in the number of episodes of vomiting during the first 24 h in patients receiving the metoclopramide combination (P = 0.0001). On first exposure to chemotherapy 45% of patients receiving dexamethasone, lorazepam and high dose metoclopramide had no vomiting while 67% had two episodes or less ('major control'). This compared to 11% total control and 25% major control in those receiving dexamethasone, lorazepam and placebo. The control of nausea in the first 24 h was also improved (P = 0.0001). There was no difference in the degree of nausea or vomiting during the following three weeks between those receiving oral dexamethasone alone and those receiving dexamethasone and metoclopramide. Both groups showed a significant increase in nausea in the three weeks following the second course of treatment when compared to the first (P = 0.0007). Extrapyramidal reactions were recorded in 11.5% of patients receiving metoclopramide. More patients stated a preference for the metoclopramide combination although this was not statistically significant (chi 2(1) = 0.29, P = 0.59). In conclusion the combination of dexamethasone and lorazepam can give major control of emesis in 25% of patients receiving very emetogenic chemotherapy. The addition of metoclopramide increases this to 67% on first exposure to chemotherapy, but at the expense of extrapyramidal reactions in 11.5%.