Chemotherapy in cancer of colon. General review

The results of surgery as sole treatment of colon cancer are summarized before dealing with those of chemotherapy. Curative or palliative chemotherapy remains controverted. The results of single drug treatments and of the conventional protocols with 5-fluorouracil and nitrosoureas have been disappointing. A promising approach is modulation of 5-fluorouracil by folinic acid, with a response rate of up to 45 p 100, and potentiation of 5-fluorouracil by cisplatin. Intra-arterial chemotherapy has been, and still is, an interesting method in liver metastases, but recent studies and the experience acquired with prolonged follow-ups have thrown doubts on some of its results, notably survival. Adjuvant chemotherapy is even more controversial than curative chemotherapy; however, a recent controlled study has yielded favourable results, and the best drug combinations have not yet been tested. It is concluded that cancers of the colon have shown some chemosensitivity, even though it has not reached the same level as that of cancers of other organs.     

比较群体化疗和目标化疗在较高感染率水平的成本─效果研究

在枞阳县凤仪乡选择感染率在12％左右的2组人群，分别实施群体化疗方案（A组）和目标化疗方案（B组），对其防治效果及实施成本进行了对比观察和分析。结果：连续实施2年，2组人群感染率分别下降69．37％和56．75％（P＞0．05）；实施成本分别为14．26元／人均和9．70元／人均；而单位效果成本，第1年B组是A组的1．4倍，第2年A组则是B组的1．8倍。提示在较高感染率水平（12％以上）的人群中宜采用群体化疗方案，而当其感染率水平降低到一定程度（8％以下）时，则应改用目标化疗方案。     

The position of neoadjuvant chemotherapy in the treatment of non-small-cell lung carcinoma

Surgical treatment of patients with non-small-cell lung carcinoma (NSCLC) offers greatest chances for long-term survival. However, the treatment is applicable only to patients diagnosed at an early stage of the disease, i.e. at stage I or II. The five year survival rate of patients operated at stage IIIA is as low as 23%. Hence there is a great need for improving survival results, especially in the sphere of systemic chemotherapy, as most tumour relapses involve the formation of metastases. Even though neoadjuvant chemotherapy in the operable stages of NSCLC still appeared very promising as a method of treatment a couple of years ago, recently published results have shown that its role has not yet been fully clarified and is still a subject of research. Additional results from randomised studies are necessary before neoadjuvant therapy may become a treatment standard. The dilemma as to whether or not to apply adjuvant, neoadjuvant or both types of chemotherapy in patients operated on for NSCLC therefore remains unsolved. On the whole, the positive role of neoadjuvant chemotherapy does not appear to be proven in the treatment of operable stage I and II NSCLS. In contrast, results of randomised studies first published in 2004 were in favour of post-surgical adjuvant chemotherapy as opposed to surgical treatment alone in NSCLC stage IB, II and IIIA. The question of whether it is better to apply chemotherapy prior to or after surgery can only be answered by the extensive randomised studies underway. The role of neoadjuvant chemotherapy in patients with NSCLC at clinical stage IIIA remains uncertain. The most rational approach to such patients appears to be neoadjuvant chemotherapy or chemotherapy with subsequent surgery.     

Myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for childhood central nervous system tumors

Myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue has been evaluated in the treatment of children and young adults with brain tumors for whom conventional therapy is either too toxic (for example, radiotherapy in infants) or ineffective (for example, recurrent malignant tumors). With this strategy, myeloablative chemotherapy is administered to patients after initial surgery, and standard-dose chemotherapy. The success of myeloablative chemotherapy depends on the histological type of tumor, extent of disease and of surgical resection, and response to prior chemotherapy. Here, we review results of myeloablative chemotherapy with hematopoietic progenitor cell rescue in brain tumors of different histologies.     

The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine in node-positive pancreatic cancer

BACKGROUND/AIMS: The effects of gemcitabine in postoperative adjuvant chemotherapy were evaluated in patients suffering from locally advanced pancreatic cancer with lymph node metastases. The results were compared with those of our historical control patients treated by surgery alone. METHODOLOGY: Twenty-one patients with node-positive pancreatic cancer who had undergone a pancreatic resection with curative intent over the five years up to February 2003, were enrolled in this study. Nine cases received postoperative adjuvant chemotherapy with biweekly administration of 1000 mg/m2 gemcitabine, while the remaining 12 cases underwent surgery without any adjuvant chemotherapy. RESULTS: The chemotherapy was well tolerated with only mild symptomatic and hematologic toxicities. The overall cumulative survival rates of the chemotherapy and surgery-alone groups were 86% and 75% at one year, and 50% and 0% at two years, with a median survival of 20.3 months and 15.4 months, respectively (p=0.0084). The disease-free interval was also significantly greater in the chemotherapy group compared with the surgery-alone group (p=0.0244). CONCLUSIONS: Adjuvant systemic chemotherapy utilizing gemcitabine was feasible with acceptable adverse effects and improved the survival rate of patients with node-positive pancreatic cancer. Although further investigation is needed to confirm these results, gemcitabine is a promising agent for the treatment of resectable advanced pancreatic cancer.     

急性粒细胞白血病化疗与体内细胞凋亡的关系

为了解白血病患者化疗期间发生体内细胞凋亡的状况。利用原位末端转移酶（ＴｄＴ）双荧光细胞流式仪法及ＤＮＡ阶梯凝胶电泳法，对１０例临床白血病患者化疗前、化疗间、化疗后的外周血单个核细胞进行了细胞凋亡的研究。结果显示：化疗前均无明显的细胞凋亡（０～２．９％），获得完全缓解和部分缓解的患者化疗期间（化疗３０～７２小时）凋亡细胞明显增高（１１．４％～７２．０％），化疗后基本未检测到凋亡细胞（０～２．９％），而４例化疗期间凋亡细胞很少出现者未达到缓解，说明有效药物才能导致细胞凋亡。用ＤＮＡ阶梯凝胶电泳法患者化疗前、中、后均未检测到ＤＮＡ“阶梯”，所以这种方法检测体内的细胞凋亡不够敏感。用原位ＴｄＴ荧光流式细胞仪，分析观察体内细胞凋亡有可能成为早期观察临床患者用药疗效的指标。     

Adjuvant chemotherapy for completely resected non-small cell lung cancer: a systematic review

PURPOSE: To conduct a systematic review and to evaluate the impact of postoperative adjuvant chemotherapy on the survival of patients with completely resected non-small cell lung cancer. METHODS: Relevant randomized trials and meta-analyses, published as articles or abstracts, were identified through electronic and hand searches by two reviewers. RESULTS: Seven meta-analyses and 26 randomized trials comparing surgery with or without chemotherapy met the pre-defined eligibility criteria for the review. The meta-analyses all showed a survival advantage for platinum- or UFT-based postoperative chemotherapy, although the results did not always achieve statistical significance. The results of individual trials were inconsistent, although recent trials have detected a large survival advantage with postoperative platinum-based chemotherapy. Differences in trial design, patient characteristics, disease stage, use of radiotherapy and chemotherapy regimen may explain the variation in results. CONCLUSIONS: Postoperative adjuvant platinum-based chemotherapy improves survival compared with surgery alone in completely resected non-small cell lung cancer. In patients fit for chemotherapy, the survival benefits strongly outweigh the adverse effects of the treatment.     

介入导管动脉化疗对直肠癌根治术后患者的疗效观察

用介入导管动脉化疗替代口服和静脉注射全身化疗治疗直肠癌根治术后患者96例。靶动脉为肠系膜上动脉、左(右)髂内动脉和肝固有动脉。治疗时间为术后2-3周、2、3、6、9、12、18、24、30、36个月。化疗药物为5-Fu、DDP 和 MMC。3年内肿瘤复发和转移21例,因肿瘤复发和转移死亡15例,其1、2、3年的生存率分别是93.8%、85.4%和82.3%。治疗中未出现大出血,肠坏死和死亡等严重并发症。结果显示介入导管动脉化疗可提高直肠癌根治术后的3年生存率,降低肿瘤的复发和转移率,安全可靠,可替代术后的口服和静脉注射全身化疗。     

术后腹腔化疗对老年结直肠癌患者生存质量的影响

目的评价老年结直肠癌患者手术后腹腔化疗对生存质量的影响。方法调查1998年1月至2002年12月期间52例60岁以上进行术后腹腔化疗的患者的生存质量GLQI指数,并与同期、同年龄段44例静脉化疗患者和40名健康老年对照组进行比较。所有病人于术前和术后6个月期间调查患者的生存质量。结果老年结直肠癌患者手术前的生存质量GLQI指数明显低于正常老年人群(P<0.05)。而两组患者手术前的生存质量GLQI指数无显著差异(P>0.05)。腹腔化疗组患者手术后6个月期间的生存质量GLQI指数高于静脉化疗组患者,其差异存在统计学意义(P<0.05)。腹腔化疗组患者手术后3月、4月、5月和6月的生存质量GLQI指数与正常老年人群无显著差异(P>0.05);而静脉化疗组患者手术后3月、4月、5月和6月的生存质量GLQI指数仍低于正常老年人群(P<0.05)。结论针对老年结直肠癌患者的生理特点,手术后采用腹腔化疗,不仅有利于提高手术后的生存期;而且有助于提高患者的生存质量,是老年结直肠癌患者手术后首选的理想化疗方式。     

Clinical evaluation of chemosensitivity testing for patients with colorectal cancer using MTT assay

PURPOSE: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. The chemosensitivity test should be performed to individualize the chemotherapy for patients with colorectal cancer, which is less sensitive for anticancer drugs. The present study was designed to determine the chemosensitivity in fresh human colorectal cancer, using highly purified tumor cells, and the correlation of this sensitivity with clinical response. METHODS: We determined the chemosensitivity for cisplatin, mitomycin C, adriamycin, and 5-fluorouracil in vitro in 93 fresh human colorectal cancers using the MTT assay and performed chemotherapy according to results of the MTT assay. RESULTS: Inhibition rate of tumor cells for cisplatin was higher than those for other drugs. Fifteen patients who have evaluable lesions received chemotherapy according to results of the MTT assay. Clinical responses were obtained in 5 of 15 patients, and the inhibition rate for cisplatin was higher in responders than in nonresponders. CONCLUSIONS: It is suggested that the chemotherapy according to results of the MTT assay is effective in patients with colorectal cancer.     

Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma

Hepatic metastases from colorectal carcinoma are common and may be resected for cure. The response of liver metastases to systemic chemotherapy is low. In contrast, hepatic arterial chemotherapy produces higher response rates than systemic chemotherapy, but randomized trials have not definitely proved a survival advantage because they allowed cross over. Most adjuvant portal vein chemotherapy studies have shown a survival advantage over the control group, but it is not clear whether this benefit is from the portal vein therapy or from immediate postoperative chemotherapy, since there is rarely a reduction in liver metastases. We describe the results of systemic, hepatic artery infusion, and portal therapy for patients with liver metastases of colorectal carcinoma.     

鄱阳湖区血吸虫病重疫区不同化疗策略的费用-效果分析

为探讨鄱阳湖血吸虫病重疫区有效、经济、简便易行的化疗策略，本文通过连续3年的现场研究，对4种化疗策略（全民化疗、全民化疗结合健康教育、Kato法筛选化疗、McAb-Dot－ELISA法筛选化疗）的费用-效果进行了比较分析，提出鄱阳湖血吸虫病重疫区在1次全民化疗后，居民血吸虫感染率下降73．1％的情况下，第2年应调整策略，采取筛选法化疗策略。     

The role of chemotherapy in locally advanced, metastatic and recurrent cervical cancer

Cervical cancer is among the major health problems world-wide although advances in screening programs. Surgery and radiotherapy are the treatment modalities of choice for early and locally advanced cervical cancer. However, the role of chemotherapy in this setting has been better investigated in the latest years. To improve loco-regional control in locally advanced disease, authors have tested both neo-adjuvant chemotherapy and concurrent chemoradiotherapy. From 1999 NCI clinical announcement, concurrent cisplatin-based chemoradiation is considered the treatment of choice for cervical cancer patients requiring radiation therapy. Neo-adjuvant chemotherapy is reaching encouraging results in IB bulky-IIA cervical cancer, but further investigation are ongoing in locally advanced cervical setting. The optimal treatment for patients with metastatic or recurrent cervical cancer is still undefined and chemotherapy is used with palliation intent. Cisplatin remains the most active cytotoxic agents, although combinations of cisplatin with paclitaxel, topotecan, vinorelbine, have shown encouraging results in phase II and in early phase III studies. This paper reviews the role of chemotherapy in the management of patients with locally advanced, metastatic and recurrent cervical cancer. Studies discussed in this paper were selected trough a search in the med-line database performed in October 2003.     

Comparative study of 3 successive treatment protocols of osteogenic osteosarcoma in children, adolescents and young adults. Apropos of 100 cases

Three therapeutic protocols were used successively for the treatment of osteogenic osteosarcoma since 1978. The first protocol associated initial surgery and 12 months of chemotherapy and was applied to 41 patients with good results in adults but poor results in children. A protocol introducing adjuvant chemotherapy based on the association of adriamycin-cisplatinum gave very disappointing results first in children and then in adults. The protocol based on HD MTX gave much more encouraging results: the long version (3 months preoperative chemotherapy) was effective in good responders but did not influence the course of poor responders. The shortened version of this protocol, derived from the T 10 Rosen protocol (1 month preoperative chemotherapy conservative surgery and appropriate peri- and postoperative chemotherapy) seems to transform the prognosis of osteosarcoma. Our current results indicate a complete primary remission rate of 89% at one year, and 83% at 33 months.     

Therapy for stage IIIB and stage IV non-small cell lung cancer

The treatment options for unresectable stage III NSCLC include definitive RT, chemotherapy, combined chemoradiotherapy, or supportive care. Compared with radiation alone or chemotherapy alone, the combination of chemotherapy and standard RT confers a modest survival benefit at the cost of increased toxicity for patients with an excellent performance status. For metastatic disease, combination chemotherapy--in particular, platinum-based regimens--improves symptom control and survival. Newer chemotherapeutic agents with higher response rates and favorable toxicity profiles are improving outcome even for the elderly and debilitated patients and those refractory to first-line chemotherapy. Evolving understanding of the molecular events in tumorigenesis is uncovering a host of promising targets for mechanism-based therapy. Many of these novel target modulators likely will require combination with conventional chemotherapy for optimal results.     

腹腔化疗对老年进展期胃癌患者术后细胞免疫的影响

目的探讨老年胃癌患者手术后腹腔化疗对免疫功能的影响。方法对我院1997年1月至2002年12月60岁及以上接受胃癌根治性手术并进行腹腔化疗的49例患者前后细胞免疫检测,并与我院同期接受胃癌根治性手术并单独行静脉化疗的37例患者进行比较,以健康老年人作为正常对照组。所有患者于化疗前1d和化疗后7d早晨空腹时静脉采血,正常对照组于体检当日早晨空腹时静脉采血,测定血清中NK细胞和T细胞亚群。结果老年胃癌患者手术后CD4 和NK细胞水平明显低于正常对照组;老年胃癌患者化疗后CD4 、CD4 /CD8 和NK细胞水平低于化疗前,静脉化疗组化疗前后的差异具有统计学意义(P<0.05),而腹腔化疗组病人化疗前后的差异无统计学意义(P>0.05)。结论针对老年胃癌患者手术后的免疫特性,宜采用对细胞免疫抑制较轻的腹腔化疗方式进行化疗。     

Feasibility of self-expandable metallic stent plus chemotherapy for metastatic gastric cancer with pyloric stenosis

Background and Aim:  Self-expandable metallic stent placement is accepted as palliative therapy for advanced gastric cancer with gastric outlet obstruction, but data are lacking for chemotherapy after self-expandable metallic stent insertion. This study retrospectively compared results between surgery plus chemotherapy and stenting plus chemotherapy for metastatic gastric cancer with pyloric stenosis.
Methods:  Subjects comprised 26 patients who received chemotherapy after surgery or endoscopic stenting for metastatic gastric cancer with pyloric stenosis between April 2000 and December 2007 in four Japanese hospitals. Patients were categorized into two groups: 15 patients who received chemotherapy after surgery for pyloric stenosis (Surgery group); and 11 patients who received chemotherapy after self-expandable metallic stent placement for pyloric stenosis (Stent group).
Results:  Median survival time and median time to treatment failure were 284 days and 226 days in the Surgery group and 337 days and 247 days in the Stent group, respectively. No significant differences were noted between survival and time to treatment failure. No significant differences were found in median oral intake rate (Surgery, 93.1%; Stent, 93.2%) or median hospital stay rate (Surgery, 24.6%; Stent, 23.7%) during survival. Response rate was 45.5% in the Surgery group and 50% in the Stent group, with no significant difference. Likewise, no significant differences were noted between groups for frequencies of toxicity or complications.
Conclusions:  The present results suggest that chemotherapy after stenting is as effective and safe as chemotherapy after surgery. Stents may replace surgery in combination therapy with chemotherapy for metastatic gastric cancer with gastric outlet obstruction.     

Chemotherapy in the treatment of neuroendocrine malignant tumors

The efficacy of chemotherapy in digestive neuroendocrine tumors (NET) depends on primary site and histological differentiation. Many reports have suggested a superior activity of chemotherapy for pancreatic NET than for metastatic carcinoid tumors with response rates ranging from 40 to 60% compared to 20%. The standard chemotherapy for pancreatic NET is a combination of adriamycin and streptozocin and to a lesser extent a combination of 5FU and streptozocin. In contrast, there is no clear standard chemotherapy for carcinoid tumors and if most oncologists use a combination of 5FU and streptozocin in the case of advanced, progressive and nonresectable carcinoid tumors, the results are mostly poor and the benefit seldom counterbalances its toxicity. In these carcinoid tumors the combination of hepatic artery ischemia alternating with chemotherapy has given impressive results in one study, which, however, have never been confirmed. Tumor cell differentiation is a major prognostic factor and some reports have suggested a higher chemosensitivity for undifferentiated or poorly differentiated NET with tumor response rates ranging from 41 to 69% when a VP16-CDDP combination is used. This chemosensitivity is, unfortunately, as in small cell lung carcinomas, of short duration. Related to this special problem and the number of other active treatments in NET, the place of chemotherapy always has to be discussed in a multidisciplinary fashion. Surgical excision, chemoembolization, interferons and somatostatin analogues have to be emphasized and eventually combined with chemotherapy, especially in slowly growing tumors. New active chemotherapy regimens have to be tested clearly in this orphan group of tumors which does not hold much interest to the pharmaceutical companies.     

Erythropoietin Response Is Inadequate in Cancer Patients Receiving Chemotherapy

The level of serum erythropoietin (EPO) is inappropriately decreased in cancer patients and has been advocated as the main cause of their anemia. In cancer patients, chemotherapy results in a cumulative anemia severe enough to require transfusion. We investigated the changes in serum EPO, hemoglobin, ceruloplasmin, and copper levels in cancer patients receiving chemotherapy. There was a weak but significant inverse relationship between hemoglobin and log[EPO] (r = -0.41; P < .001). Observed/expected serum EPO ratios decline with repeated chemotherapy indicating inadequate EPO response for the degree of anemia. There was no difference in the severity of anemia and in the degree of EPO response between platinum- and non-platinum-treated patients. Ceruloplasmin, copper, and ferritin levels did not change during chemotherapy. Our results suggest that the EPO response is inadequate for the degree of anemia and justifies the use of recombinant human EPO in cancer patients receiving chemotherapy.