Gastric and gastro-oesophageal cancer therapy

Gastric and gastro-oesophageal cancers represent a global health problem. In recent years, there has been a marked increase in the incidence of proximal gastric and distal oesophageal adenocarcinomas. Surgery is the primary therapy for localised gastric or gastro-oesophageal cancer; however, patients treated with surgery have high rates of local and distant relapse as well as an unacceptably low 5-year survival rate. Chemoradiation and preoperative chemotherapy can play an important role for these patients. The outcome of patients with metastatic disease is very poor but a number of newer chemotherapy agents, such as docetaxel, oxaliplatin and S-1, have been identified and some have shown promising results. This article reviews recent trials on localised and metastatic gastric and gastro-oesophageal cancers.     

Gastric and gastro-oesophageal cancer therapy

Gastric and gastro-oesophageal cancers represent a global health problem. In recent years, there has been a marked increase in the incidence of proximal gastric and distal oesophageal adenocarcinomas. Surgery is the primary therapy for localised gastric or gastro-oesophageal cancer; however, patients treated with surgery have high rates of local and distant relapse as well as an unacceptably low 5-year survival rate. Chemoradiation and preoperative chemotherapy can play an important role for these patients. The outcome of patients with metastatic disease is very poor but a number of newer chemotherapy agents, such as docetaxel, oxaliplatin and S-1, have been identified and some have shown promising results. This article reviews recent trials on localised and metastatic gastric and gastro-oesophageal cancers.     

Neoadjuvant chemotherapy in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a systemic illness. More than half of those patients who present with stage I-IIIA disease and are resected will experience distant relapse. Postoperative adjuvant chemotherapy has been evaluated in several randomized trials but the results of these trials have been inconclusive with increased survival reported in few trials. In resectable stage IIIA NSCLC the findings of three randomized trials have indicated that the survival of these patients is better with neoadjuvant chemotherapy plus surgical resection than with resection alone. Phase II trials using preoperative concurrent chemoradiotherapy have been carried out with encouraging results. The majority of patients with stage IIIA NSCLC require multimodality therapy if they are to achieve a 5-year survival. Combined modality treatment in locally advanced NSCLC continues to evolve and is a subject of ongoing research. One focus for present research is to integrate new active agents into the neoadjuvant setting. Another challenge is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible, does not appear to compromise surgery and yields high response rates. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse.     

早期乳腺癌保乳治疗对照试验远期疗效的荟萃分析

目的：系统评价国内早期乳腺癌保乳手术治疗（BCT）与改良根治术（MRM）对照的远期疗效。方法检索2006～2013年收集已发表的关于早期乳腺癌保乳治疗与改良根治术对照试验的国内文献,针对结果进行统计学综合（Meta）分析。采用优势比（OR）及95%置信区间（95%CI）描述效应量。以3年生存率、局部复发率、远处转移率进行综合评价早期乳腺癌手术现状。结果27篇中文文献符合纳入标准,包括1136例保乳手术患者和1325例改良根治术手术患者;（1）3年生存率指标对比,差异无统计学意义（P＞0.05）,提示保乳组手术与改良根治术组3年无病生存率无差别;（2）3年局部复发率比较,差异无统计学意义（P＞0.05）,即认为保乳组3年局部复发率与改良根治术组相当;（3）对3年肿瘤远处转移指标进行分析,差异无统计学意义（P＞0.05）,提示保乳组与改良根治术组在3年肿瘤远处转移率上无明显区别。结论保乳手术与改良根治术具有相同的远期疗效,保乳手术具有创伤性小、术后恢复快,美观,有效提高生存质量,可作为早期乳腺癌治疗的首选。     

Neoadjuvant chemotherapy and chemoradiotherapy for non-small cell lung cancer: current status and future prospects

Of the patients with non-small cell lung cancer, 60% present with localised or locally advanced disease. Although they may be considered potentially curable, the vast majority will die, usually from systemic disease. So far, adjuvant (postoperative) therapy has failed to demonstrate benefit. In contrast, chemotherapy has demonstrated clear advantages when administered prior to, or concurrently with radiotherapy in Stage III disease or prior to surgery in Stage III disease. Chemotherapy administered prior to surgery, termed neoadjuvant therapy, in Stage I and II disease has been demonstrated to be feasible. Several trials employing currently available agents have yielded promising results. Whether these regimens will result in an unequivocal benefit is the subject of several ongoing studies in the US and Europe. Current research is focusing on the role of newer drugs including novel antitubulin agents, growth factor receptor antagonists, eicosanoid modulators and various other agents.     

Neoadjuvant chemotherapy and chemoradiotherapy for non-small cell lung cancer: current status and future prospects

Of the patients with non-small cell lung cancer, 60% present with localised or locally advanced disease. Although they may be considered potentially curable, the vast majority will die, usually from systemic disease. So far, adjuvant (postoperative) therapy has failed to demonstrate benefit. In contrast, chemotherapy has demonstrated clear advantages when administered prior to, or concurrently with radiotherapy in Stage III disease or prior to surgery in Stage III disease. Chemotherapy administered prior to surgery, termed neoadjuvant therapy, in Stage I and II disease has been demonstrated to be feasible. Several trials employing currently available agents have yielded promising results. Whether these regimens will result in an unequivocal benefit is the subject of several ongoing studies in the US and Europe. Current research is focusing on the role of newer drugs including novel antitubulin agents, growth factor receptor antagonists, eicosanoid modulators and various other agents.     

Clinical trials with fluorinated pyrimidines in patients with head and neck cancer

Summary While it is estimated to be one of the most prevalent cancers in the world, cancer of the head and neck is an uncommon malignant tumor in the United States and accounts for only 5% of all malignancies [1]. Head and neck cancer is a term that encompasses heterogeneous groups of patients. The most common histologic type is the squamous cell carcinoma. Cancer of the oral cavity is the most common site among the head and neck tumors. The majority of patients (70–80%) present with locally advanced (Stage III and IV) cancer. The standard treatments of surgery and/or radiotherapy have a high cure rate for patients with early disease (Stages I or II), but not for patients with locally advanced tumors. Local recurrence and persistent disease occur in more than 60% of patients present with advanced cancer, and approximately 10%–20% of all patients develop distant metastases [2–9].Chemotherapy is usually used for palliation in patients with recurrent and metastatic head and neck cancer at which time these patients have failed the definitive therapy of surgery and/or radiotherapy and the chances for salvage is almost nil. With the identification of more active cytotoxic agent(s) and combinations, chemotherapy is being investigated as part of multi-modality treatment in patients with previously untreated and locally advanced head and neck cancer [2,10].     

Neoadjuvant chemotherapy of breast cancer

About 80% of patients with breast cancer ultimately die of metastatic disease at 20 years. Distant metastases are more important as a cause of death than local or regional relapses. It is for this reason that adjuvant chemotherapy is necessary, especially in young patients and those with extensive disease. Initial chemotherapy preceding any local or regional treatment is justified on the grounds that both surgery and anaesthesia lead to immunodepression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials by Nissen-Meyer, Bonadonna and Cooper (1-3). In the present study 145 patients, including 67 with inflammatory breast cancer (IBC), were treated with 4-6 weeks of Velbe, thiotepa, methotrexate, fluorouracil and prednisone, with Adriblastin added for patients with IBC, T greater than 7 cm, or N2, N3. Because of tumour regression of greater than 50% observed in 80% of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium), resulting in complete remission in all these cases. Maintenance treatment with the same drugs was prescribed for 6-18 months depending on the initial stage. Tumour regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest being 42 months. Overall survival at 2 years for IBC is 90%, with a disease-free survival of 80%. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.     

Adjuvant chemotherapy for non-small cell lung cancer: a New Zealand perspective

This article reviews recent developments with the use of adjuvant chemotherapy for resected early-stage non-small cell lung cancer (NSCLC) and the implications of these developments for healthcare in New Zealand (NZ). Non-small cell lung cancer is a major cause of mortality and morbidity in NZ, and is greatly over-represented among Maori and socioeconomically deprived populations. Early-stage NSCLC is potentially curable by surgery, but long-term outcome after surgical resection is limited by disease recurrence locally or at sites distant from the primary disease. Three recent large randomised controlled phase III trials using modern platinum-based combination chemotherapy protocols have shown significant survival benefits for the use of postoperative adjuvant chemotherapy after resection of early-stage NSCLC. Cisplatin plus vinorelbine was used as the adjuvant chemotherapy regimen in two of these trials resulting in improvements in 5-year survival of 51.2% versus 42.6% (p=0.013) and 69% versus 54% (p=0.03), respectively. In NZ, adjuvant chemotherapy for NSCLC is expected to prevent up to 15 lung cancer deaths each year for relatively low drug expenditure and has the potential to benefit Maori and the economically-deprived disproportionately more than other populations. In conclusion, it is the opinion of this group of NZ lung cancer specialists that adjuvant chemotherapy with cisplatin plus vinorelbine should now be adopted as a standard of care for patients with resected stage II and III NSCLC. For this to occur, current PHARMAC policies preventing its use for these eligible patients will need to be revised.     

Current chemotherapy options for thymic epithelial neoplasms

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.     

Current chemotherapy options for thymic epithelial neoplasms

Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the cornerstone of effective therapy. Stage I disease is effectively treated by complete surgical resection. The role of radiation therapy in completely resected stage II disease remains controversial. Adjuvant radiation therapy is useful for local control and may improve survival in patients with incompletely resected tumours. Cisplatin-based chemotherapy regimens play an important role in the treatment of advanced stage III/IV or recurrent disease thymomas, but have proven less effective for thymic carcinoma. Phase II trials of multimodality therapy incorporating neoadjuvant chemotherapy, surgery and postoperative radiation therapy show promise for unresectable disease. This review discusses recent clinical data and the potential role for agents targeting the epidermal growth factor receptor, angiogenesis and apoptotic pathways.     

Treatment of non-localised, non-metastatic rectal cancer

The standard treatment for rectal cancer is surgical removal of the rectum and mesorectum. Is the prognosis for non-metastatic rectal cancer that extends beyond the bowel wall improved by adding radiotherapy and/or chemotherapy to surgery? To answer this question, we conducted a review of the literature using the standard Prescrire methodology. Randomised trials conducted before optimal surgery was developed showed that, compared with surgery alone, postoperative radiotherapy reduced the risk of local recurrence and possibly increased overall survival. In the only randomised trial in which the mesorectum was systematically removed, preoperative radiotherapy had no impact on overall survival but reduced the risk of local recurrence (5% at 10 years, versus 11% without radiation therapy).This result was statistically significant in patients with lymph node involvement. Radiotherapy for rectal cancer carries a risk of faecal incontinence (about 50% of patients), small bowel occlusion, and secondary cancers (about 1 in 15 patients). In patients who receive neither radiotherapy nor chemotherapy before surgery, postoperative chemotherapy based on fluorouracil or the tegafur + uracil combination increases overall survival by about 5% at 5 years, in absolute numbers, but carries a risk of serious adverse effects, including haematological and gastrointestinal disorders. Eight randomised trials suggest that the beneficial effects of post-operative chemotherapy and radiotherapy persist and are additive. However, the same is true for adverse effects. In four randomised trials, adding chemotherapy to preoperative radiotherapy roughly halved the risk of local recurrence. In three randomised trials, preoperative chemoradiotherapy appeared to be slightly more effective than postoperative chemoradiotherapy in terms of recurrence, and to carry a similar or lower risk of serious adverse effects, without improving overall survival. Preoperative chemoradiotherapy carries a risk of unnecessarily exposing between 8% and 18% of patients to adverse effects, as their tumour is found to be less extensive than initially thought. There is no firm evidence that postoperative chemotherapy is beneficial after preoperative radiotherapy. Preoperative treatments do not prevent removal of the anal sphincter. The probable benefits of adjuvant therapies in surgical patients must be weighed, on a case by case basis, against the potential risk of serious adverse effects and complications.     

Conventional cytotoxic and novel therapeutic concepts in colorectal cancer

Colorectal cancer (CRC) is a major cause of death, particularly in the Western world, leading to 400,000 deaths each year [1]. Of the patients, 30% have advanced disease at presentation, either locally or at distant sites and chemotherapy in this setting has an established role in improving survival and palliating symptoms [2]. In addition, approximately 50% of those patients initially believed to be cured by surgery, subsequently relapse and die of their disease. Adjuvant chemotherapy administered for six months after surgery for Dukes C colon cancer improves absolute survival by 5 - 10% [3]. However, the role of adjuvant chemotherapy in Dukes B colon or Dukes B/C rectal tumours is still controversial and is only recommended within the scope of a randomised clinical trial. Cytotoxic drug development for colorectal cancer has traditionally followed the established pathway of Phase I, Phase II and then Phase III trials in advanced disease, with subsequent translation into the adjuvant setting. For the purpose of this review current conventional chemotherapy for advanced CRC is described, followed by an explanation of newer developments that are predicated upon our increasing understanding of the molecular processes underpinning malignant transformation, invasion and metastasis. Paradigm shifts in trial design necessitated by a mechanistic approach to drug development are also discussed.     

保乳手术与改良根治术治疗早期乳腺癌的临床疗效观察

目的：探讨保乳手术与改良根治术治疗早期乳腺癌的临床效果。方法回顾性分析2009年11月～2011年6月本院收治的早期乳腺癌行保乳手术的患者45例为观察组,选择同期行改良根治术的早期乳腺癌患者45例为对照组,比较两组患者的手术效果,术后并发症的发生率,美容效果满意率,5年生存率,局部复发率及远处转移率等情况。结果观察组患者手术时间、术中出血量,住院时间及术后并发症的发生率均少于对照组（P＜0.05）。观察组患者美容效果优良率明显高于其对照组（P＜0.05）;两组患者5年生存率,局部复发率和远处转移率比较,差异无统计学意义（P＞0.05）。结论早期乳腺癌保乳手术治疗效果明显优于改良根治术,具有手术时间短,创伤小,术中出血少,美容效果好及术后并发症少等优点,值得临床推广应用。     

腹腔镜手术应用于不同分期结肠癌的临床疗效分析

目的探讨腹腔镜手术应用于不同分期结肠癌患者的临床疗效。方法选择2010年4月～2011年7月我院收治的180例结肠癌患者,将其随机分为观察组和对照组,每组90例,观察组患者采用腹腔镜手术治疗,对照组患者采用开腹手术进行治疗,比较两组患者的肿瘤分期及治疗后的远处转移、局部复发和远期并发症情况。结果对照组患者术后切口疝和肠梗阻等远期并发症的发生率均明显高于观察组（P〈0．05）,而两组患者的远处转移、局部复发率及术后1年生存率差异无统计学意义（P〉0．05）。结论腹腔镜结肠癌手术应用于各分期的结肠癌患者均可获得较好的临床疗效,且远期并发症发生率降低,值得临床推广应用。     

Trials of adjuvant chemotherapy in colorectal cancer

Chemotherapy has been extensively investigated in colorectal cancer. Evaluation in advanced disease has shown that only a limited number of drugs are active. This activity was assessed according to objective criteria for response of measurable lesions, but despite producing objective remissions, no agent has prolonged survival in advanced disease. Drugs showing activity in advanced disease have been evaluated subsequently as adjuvants to surgery. Single agents were evaluated first and 5-fluorouracil has been investigated most extensively. It has been administered by a variety of routes and in different regimens and in some trials it has produced results which border on statistical significance for both disease-free interval and survival. It is the drug of first choice in colorectal cancer, although in some trials no effect was seen. Razoxane (ICRF 159) has also been evaluated and has shown some promise, although also some toxicity. Trials of combinations of treatments have been performed and have used permutations of 5-fluorouracil, MeCCNU, BCG and radiotherapy. None of these trials has shown a definite advantage for chemotherapy and, in some, toxicity has been considerable. 5-Fluorouracil as a single agent has shown the best results to date, and is the treatment of first choice but no treatment has been shown to prolong survival unequivocally in colorectal cancer. Future trials should include a surgery-only control arm, against which any new treatment can be compared.     

Neoadjuvant strategies in the treatment of non-small cell lung cancer

The prognosis of patients with resectable non-small cell lung cancer (NSCLC), other than stage IA disease, remains disappointing, with 5 year survival rates ranging from 40-55%. For the past 15-20 years, several phase II trials have investigated the efficacy of chemotherapy and chemoradiotherapy prior to surgery in the management of stage IIIA NSCLC, with encouraging results. Phase III trials comparing surgery alone with chemotherapy plus surgery have confirmed the efficacy of this multimodality approach. Gemcitabine, one of the new agents with significant activity against NSCLC, has undergone extensive clinical testing in combination with cisplatin in this setting. In 47 patients with stage IIIA disease, induction with gemcitabine/cisplatin was well tolerated and yielded a response rate of >70%. Downstaging of the mediastinal lymph nodes occurred in 53% of patients. Preliminary data from another study employing mitomycin C, ifosfamide and cisplatin in resectable NSCLC suggest that there are favourable effects of induction treatment, especially in early-stage disease. With the availability of chemotherapeutic combinations such as gemcitabine/cisplatin, which are both effective and well tolerated, combination therapy is likely to become a major advance in the treatment of patients with early-stage (IB, II) NSCLC.     

Treatment of PSA only recurrence of prostate cancer after prior local therapy

Prostate cancer recurrence (after prior local treatment) that is detectable only by a rise in serum prostate specific antigen (PSA) level is a very common problem facing clinicians. Given that the majority of contemporary era men with PSA-only or biochemical recurrence are relatively young and otherwise healthy, treatment requires approaches that both improve clinical outcomes and preserve quality of life. Treatment is in one of two broad categories, additional local therapies, termed "salvage" local therapy and systemic therapies. For radical prostatectomy patients, salvage external beam radiotherapy to the prostate bed is commonly employed, being reserved for early biochemical recurrence in men with low risk at distant metastases. For primary radiation patients, salvage radical prostatectomy or cryotherapy can similarly be used for those men felt not to harbor distant metastases. Systemic therapy generally involves hormonal therapy. Traditional hormonal therapy (orchiectomy, luteinizing hormone-releasing hormone agonists or maximum androgen blockade) is the current mainstay of systemic treatment for biochemical recurrence, although non-traditional approaches, such as antiandrogen monotherapy, are increasingly being used. There is a critical need for new pharmaceutical agents to treat this growing stage of prostate cancer. However, it has been difficult to demonstrate efficacy due to the long natural history until death and the survival endpoint currently required by the U.S. Food and Drug Administration. New data show that PSA Doubling time (PSA-DT) during PSA recurrence may be a valid surrogate for death from the disease and may be used to accelerate drug approval. This monograph will attempt to provide a complete balanced discussion of the evaluation and treatment of biochemical recurrence of prostate cancer after prior primary local therapy.     

结直肠癌腹腔镜手术与开放手术远期疗效与安全性分析

目的探究结直肠癌腹腔镜手术与开放手术的远期疗效与安全性。方法选取医院2008～2010年结直肠癌患者60例,腹腔镜组30例,开放手术组30例,随访观察远期治疗效果与安全性。结果两组患者在局部复发、远处转移、穿刺孔和小切口肿瘤种植转移、复发率、3年生存率、5年生存率指标上差异无统计学意义(P>0.05)。结论结直肠癌腹腔镜手术的远期治疗效果和安全性能与开放手术达到相似的效果。     

Emerging treatments for ovarian cancer

The survival at 5 years, of patients with ovarian cancer, has steadily improved since 1960, when surgery and alkylating agents were the only initial modalities employed to cope with the usual late presentation of the disease. In the 1980s, cisplatin and then carboplatin became established as the most active drugs, alone or in combination with other drugs. In the last decade, the antimicrotubulin drug paclitaxel, and the topoisomerase I inhibitor topotecan were noted to be active after failure of platinum drugs. These drugs, as well as others with known activity in the second-line setting, such as the pegylated liposomal doxorubicin, gemcitabine and oral etoposide, all play a role in the treatment of these patients and likely prolong survival without eradicating the disease. The plight of these patients has stimulated new areas of drug development. Here, the evolution of the current therapeutic strategy, the scientific rationale for cytotoxic and non-cytotoxic agents and their status at present are reviewed. 'Targeted' drug trials, in contrast to trials studying cytotoxic drug analogues, currently represent only a minor portion of clinical trials in ovarian cancer.