晚期非小细胞肺癌化疗现状及进展

晚期非小细胞肺癌 (ＮＳＣＬＣ)包括不能手术切除的ⅢＢ、Ⅳ期和术后、放疗后复发转移者。患者预后极差 ,中位生存期 (ＭＳ)仅 16～ 17周 ,1年生存率为 10 %～ 15% [1,2 ] 。 80年代起 ,顺铂 (ＤＤＰ)、卡铂 (Ｃａｒｂｏ)、异环磷酰胺 (ＩＦＯ )、长春花碱酰胺 (ＶＤＳ)、丝裂霉素(ＭＭＣ)、足叶乙甙 (ＶＰ16)和替尼泊甙 (ＶＭ2 6)等的相继出现为晚期ＮＳＣＬＣ的治疗带来一些希望 ,但单药有效率均低于 15%。有作者对 52个随机临床试验的ＭＥＴＡ分析显示 ,联合化疗优于单一用药 ,含铂类的化疗方案能提高生存期、缓解全身症状及改善生活质量…     

Current status of chemotherapy for gastric cancer

High response rates to combination chemotherapy reported by the end of the seventies led many oncologists to recommend standard treatment for gastric cancer. In randomized trials conducted by different groups, the response rate with fluorouracil (F), adriamycin (A), mitomycin C (M) ranged between 17 and 39% and was advocated for adjuvant treatment. However, further studies indicate that combination chemotherapy has no beneficial effect on survival compared with 5-FU alone. Several studies assessing the FAM regimen versus control in the adjuvant setting show, so far, no difference between the treatment arms.Other agents and combinations have recently been investigated. Cisplatin (P) is active in gastric cancer. In six studies using a combination with FA (FAP), the response rate ranged between 29 and 55% with a median survival of 4–12 months. Other combinations using P with F or etoposide and A have also been promising. Recently, the EORTC Gastrointestinal Group, using a combination of sequence of high dose methotrexate and F with A (FAMTX) reported 22 positive responses out of 66 eligible patients, including nine complete responders. These new treatments are currently being tested by different groups in a randomized trial. For the time being, apart from 5-FU alone, chemotherapy in advanced gastric cancer should not be administered on a routine basis outside clinical trials.     

Current status of adjuvant chemotherapy for breast cancer

Breast cancer is one of the most common malignancies among Japanese women. Approximately 40,000 new patients are diagnosed annually. In the USA, however,the mortality from breast cancer has recently been declining. A nationwide screening promotion using mammography, and recent advances in the treatment for early breast cancer have been the main reasons. It was widely accepted that for breast cancer as a systemic disease, appropriate systemic treatment of either chemotherapy and endocrine therapy improved the survival. We describe here the contributions of new agents to the improvement in survival for breast cancer patients and introduced the concept of dose density.     

Current status of adjuvant chemotherapy for gastric cancer

Although radical gastrectomy is a standard treatment for advanced gastric cancer, recurrence remains high. After several large-scale controlled studies have shown the beneficial effects of adjuvant chemotherapy, that treatment emerged as a standard option for advanced gastric cancer after gastrectomy. However, various guidelines from different countries have suggested different adjuvant chemotherapies. Understanding the differences between guidelines is very important for investigating further therapeutic strategies. Fortunately, because there are many ongoing studies about new regimens for adjuvant treatment, it is expected that patients with gastric cancer after surgery will have better outcome.     

Current status of dose-dense chemotherapy for breast cancer

In an effort to improve the effectiveness of chemotherapy for breast cancer, examination of the impact of dose intensity, dose density, and treatment duration may have as much relevance as the specific antineoplastic agents utilized. After several years of pilot feasibility studies of dose-dense chemotherapy regimens, whose delivery has been made safe and feasible by the use of hematopoietic growth factor support (in particular, filgrastim), we now have phase III data demonstrating the advantages of this approach in the adjuvant treatment of breast cancer.     

Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial

Adjuvant chemotherapy after resection of stage II-IIIA non-small-cell lung cancer is now the standard of care based on the results of 3 phase III studies using cisplatin-based regimens, IALT (International Adjuvant Lung Trial), The National Cancer Institute of Canada JBR.10, and ANITA (Adjuvant Navelbine International Trialist Association). The role of adjuvant chemotherapy for stage IB disease remains controversial, even more so now that the updated results from CALGB (Cancer and Leukemia Group B) trial 9633 are statistically negative. CALGB 9633 was the only randomized adjuvant trial to use a carboplatin backbone and focused exclusively on patients with stage IB disease. Initial results, reported in 2004, showed a significant survival advantage with the addition of chemotherapy, but the 2006 updated results are no longer statistically significant. The next large intergroup adjuvant trial in non-small-cell lung cancer will look at bevacizumab in combination with chemotherapy. Because of the recent update, this trial will now limit patients with stage IB disease to those with larger tumors (>or= 4 cm) and will likely include only cisplatin-based regimens.     

Current status and perspectives in cancer chemotherapy

New anticancer drugs with novel structures including paclitaxel, docetaxel, ilinotecan and gemcitabine have shown significant activity against various solid tumors in phase II trials. Phase II trials of combination regimens containing these drugs are currently in progress. Some combinations such as paclitaxel plus cisplatin in ovarian cancer have shown superiority over the past standard regimen. Not surprisingly, several analogues of these drugs have been developed and currently phase II trials are in progress. ET-743 may has some hope to become the first anticancer drug from a marine product. Oral chemotherapy is useful for treatment of outpatients. A combination regimen of UFT plus oral leucovorin has shown equivalent activity to 5-fluorouracil and leucovorin in advanced colorectal cancer, and capecitabine has shown superior activity and less toxicity than 5-fluorouracil and leucovorin in advanced colorectal cancer. Monoclonal antibody therapy has been successful in patients with breast cancer overexpressing HER2 and in patients with B-cell lymphoma. Currently clinical trials of 17-1A for colorectal cancer and HUM195 for acute myelogeneous leukemia are in progress. Recently presented results of angiogenesis inhibitors are discussed.     

Current status of chemotherapy for advanced colorectal cancer in Japan

Treatment policies for metastatic colorectal cancer (CRC; mCRC) are similar in Japan and in Western countries. An important goal is the global development of new molecular-targeted drugs. To achieve this goal, controlled clinical trials should be performed to determine whether S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, can replace 5-fluorouracil for the treatment of CRC. On the other hand, the use of adjuvant chemotherapy differs slightly between Japan and Western countries. An underlying reason is the difference in surgical results. In Japan, the use of adjuvant chemotherapy with oral fluoropyrimidines evolved independently from developments in Western countries. However, clinical studies of adjuvant chemotherapy require more patients and longer follow-up periods than clinical studies of mCRC. The use of international collaborative clinical trials is essential to ensure that more effective drugs will be promptly provided to patients in every country. Improved quality control of surgery in patients participating in clinical trials or a better collective understanding of the quality of centers performing such studies will most likely facilitate the design of international collaborative clinical trials. International meetings, including the participation of oncologists and surgeons, should be held in the near future to promote collective understanding and the design of high-quality clinical studies.     

Current status of chemotherapy for advanced pancreatic and gastric cancer

There is currently no effective systemic therapy for advanced pancreatic cancer. No definitive controlled data exist that demonstrate a survival benefit for any particular regimen yet developed. A statistically significant short-term survival benefit has been seen in three consecutive GITSG trials using the FAMe regimen in patients with advanced gastric cancer. Occasional long-term responders have been seen with a variety of regimens, but there is no evidence of improved long-term (more than two years) disease-free survival with any regimen reported to date. Continuing research with emphasis on new drug development, innovative alterations in chemotherapy combinations and administration schedules, or entirely new treatment strategies, are clearly required to allow the clinical investigator and the clinical practitioner to achieve their common goal--improved long-term survival for patients with advanced pancreatic and gastric cancer.     

宫颈癌新辅助化疗的现状与争议宫颈癌新辅助化疗的现状与争议

针对新辅助化疗研究的现状及存在的问题,通过查找几年来关于宫颈癌新辅助化疗的相关文献显示,宫颈癌发病率逐年呈上升趋势。其治疗手段目前仍以手术、放疗、化疗为主,治疗效果并无明显提高,尤其中晚期或复发的患者5年生存率更低。新的化疗药物的研究对宫颈癌治疗有一定疗效,宫颈癌的化学治疗越来越受到国内外学者的重视。新辅助化疗(neoadjuvant chemotherapy,NACT)的出现在很大程度上改善了患者的预后,提高了患者存活率。     

Current status of stereotactic body radiotherapy for lung cancer

Stereotactic radiotherapy (SRT) for extracranial tumors has been recently performed to treat lung and liver cancers, and has subsequently been named stereotactic body radiotherapy (SBRT). The advantages of hypofractionated radiotherapy for treating lung tumors are a shortened treatment course that requires fewer trips to the clinic than a conventional program, and the adoption of a smaller irradiated volume allowed by greater setup precision. This treatment is possible because the lung and liver are considered parallel organs at risk. The preliminary clinical results, mostly reported on lung cancer, have been very promising, including a local control rate of more than 90%, and a relatively low complication rate. The final results of a few clinical trials are awaited. SBRT may be useful for the treatment of stage I lung tumors.     

Current status of adjuvant chemotherapy of gastric cancer

Effect of adjuvant chemotherapy on the postoperative survival of gastric cancer patients has been suggested by various clinical trials with an aim of controlling minimum residual tumors after surgery. Incorporation of adjuvant chemotherapy with MMC, 5-FU, FT-207, or immunomodulators into the treatment modalities might be one of the basic treatment strategies for gastric cancer. Well designed, controlled trials in terms of selecting proper drugs and patients, and of statistical methodology, are essential for the proper evaluation of the adjuvant chemotherapy.     

Current status of chemotherapy in metastatic pancreatic cancer

The role of chemotherapy, and especially the experience of the EORTC Gastrointestinal Group with this treatment, in advanced pancreatic cancer is discussed. Combination chemotherapy is not superior to single agents and to date chemotherapy in this disease must be considered as experimental. There is no standard treatment available and patients should only be treated in clinical trials.     

Current status and future perspectives in chemotherapy for testicular cancer

Approximately eighty percent of patients with disseminated testicular cancer can currently be cured because of the progress in cisplatin-based chemotherapy. For good risk disseminated disease, three courses of bleomycin, etoposide and cisplatin (BEP) is the most reliable induction chemotherapy. Cisplatin, ifostamide and either etoposide or vinblastine (VIP or VeIP) is effective standard-dose salvage chemotherapy, especially for relapsed patients with good prognosis features. However, remission is of short duration in many cases, resulting in an overall long-term disease-free survival rate of 10% to 25%. One possible approach to improve outcome is drug-dose increment. In recent years, high-dose chemotherapy (HDCT) with autologous stem-cell rescue has been used with some success in the first relapse cases and refractory cases. Although these non-randomized data are promising, the clinical benefit of HDCT remains to be confirmed in an ongoing randomized study. Another strategy is to include a new active drug in the chemotherapy regimen. Recent studies combining new active agents such as paclitaxel, gemcitabine and irinotecan have showed promising results in patients with poor prognostic disease or as salvage therapy.     

Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer

Muscle-invasive transitional cell carcinoma occurs in approximately 30% of patients and is associated with a high risk of distant metastasis. Radical local therapy in the form of cystectomy or radiotherapy is curative in a portion of patients. Systemic therapy to treat occult micrometastasis at the time of local control is necessary to improve outcomes. Neoadjuvant chemotherapy is associated with a 5-6% improvement in overall survival at 5 years, and adjuvant chemotherapy may achieve similar results, although this remains unproven. Operative complications are not increased with neoadjuvant therapy. Perioperative treatment strategies remain underutilized, and many patients are not offered treatment to reduce the risk of relapse. Neoadjuvant strategies are a potent tool for research and should be employed to test new agents for the treatment of transitional cell carcinoma.     

Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer

Muscle-invasive transitional cell carcinoma occurs in approximately 30% of patients and is associated with a high risk of distant metastasis. Radical local therapy in the form of cystectomy or radiotherapy is curative in a portion of patients. Systemic therapy to treat occult micrometastasis at the time of local control is necessary to improve outcomes. Neoadjuvant chemotherapy is associated with a 5–6% improvement in overall survival at 5 years, and adjuvant chemotherapy may achieve similar results, although this remains unproven. Operative complications are not increased with neoadjuvant therapy. Perioperative treatment strategies remain underutilized, and many patients are not offered treatment to reduce the risk of relapse. Neoadjuvant strategies are a potent tool for research and should be employed to test new agents for the treatment of transitional cell carcinoma.     

非小细胞肺癌抗血管生成治疗研究现状

血管生成是指从已有血管网络中生成新生血管的生理过程.在肿瘤微环境中,一个不断增长的肿瘤的动态平衡有利于转向持续促血管生成状态.自人类认识到可以通过抵抗肿瘤血管生成从而抑制肿瘤生长后,抗血管生成药物应运而生并已被应用在多种实体肿瘤中,包括肺癌.本文就肿瘤血管生成以及非小细胞肺癌抗血管生成的研究现状进行综述.     

非小细胞肺癌的联合免疫治疗现状

对于晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的患者来说,化疗、放疗、靶向治疗及抗血管生成治疗虽然可以改善其预后,但经相关研究发现,NSCLC患者的5年生存率仍不尽人意。近年来以程序性死亡蛋白1（programmed cell death protein 1,PD-1）/程序性死亡蛋白配体1（programmed death-ligand 1,PD-L1）抑制剂为代表免疫检查点抑制剂的出现为晚期NSCLC患者的治疗带来了新的希望。探索免疫检查点抑制剂联合化疗、抗血管生成药物、放疗的各项治疗策略是目前肿瘤界的热门话题,本文将对NSCLC联合免疫治疗的现状进行总结与讨论。