Combination therapy versus single agent chemotherapy in non-small cell lung cancer

There is proven evidence of improved symptom control with platinum-based chemotherapy in the palliation of non-small cell lung cancer, and small but definite improvements in progression-free and overall survival when compared with best supportive care. The newer chemotherapy agents vinorelbine, gemcitabine, docetaxel and paclitaxel all have single agent activity, and in combination with cisplatin these provide superior quality of life and/or survival compared with the single agents, albeit with some increase in haematological toxicity. Doublet chemotherapy consisting of a new agent combined with platinum, cisplatin by preference where tolerated, has become the standard of care for advanced disease. The use of a functional assessment of fitness, rather than chronological age alone, is appropriate in the treatment of elderly patients. Although in this group there is evidence that doublets are superior to single agents, treatment should be undertaken with caution. In the second line setting where patients are unlikely to tolerate combination therapy, single agents have proven superiority over best supportive care. Patients with poor performance status (PS2) without comorbidity may tolerate combination therapy, but currently available evidence is insufficient to allow a definitive recommendation for combination or single-agent chemotherapy.     

Is there a role for vindesine in the treatment of non-small cell lung cancer?

Summary Vindesine is a semisynthetic derivative of vinblastine which has been evaluated in clinical studies since the late 1970's. The literature on vindesine in the treatment of non-small cell lung cancer has been reviewed and all aspects of vindesine treatment in this disease has been covered. It is concluded that vindesine as a single agent yields a response rate of 18% based on the treatment of 295 patients included in phase II trials (95% confidence limits 13%–22%). No difference was observed among the three major histologic types of non-small cell lung cancer. In phase III trials, the response rate and confidence limits are at a similar level. Combination chemotherapy including vindesine plus cisplatin ranks among the most active treatments in non-small cell lung cancer and is as active as etoposide plus cisplatin, both with respect to response rate and survival. It has not been documented that the addition of one or two other drugs to the combination of vindesine yields an increase in survival. When best supportive care was compared with a combination of vindesine plus cisplatin, the group with chemotherapy was attributed a survival advantage in all three studies published, and the difference was statistically significant in two of these three studies. Thus, vindesine has a well documented activity in non-small cell lung cancer and ranks among the most active single agents in this disease. Vindesine is also part of several active combination chemotherapies among which the combination of vindesine plus cisplatin is particularly interesting, because it has been repeatedly shown to prolong survival as compared to supportive care. Especially this latter point leads to the conclusion that there is a role for vindesine in the treatment of non-small cell lung cancer. However, the concept of chemotherapy in this disease remains investigational even though the advances seen in recent years clearly merit further studies.     

Chemotherapy of non-small cell lung cancer in elderly patients

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed over the age of 65 and approximately one-third of all patients with non-small cell lung cancer (NSCLC) are over the age of 70. Elderly patients tolerate chemotherapy poorly as compared to their younger counterparts, because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy, the standard medical treatment of advanced NSCLC. At present, for early stages of the disease there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemo-radiotherapy in locally advanced disease increases toxicity and seems to determine no survival advantage as compared to the radiation therapy alone. In advanced disease, single agent vinorelbine has proven to be active and well-tolerated, and compared to best supportive care, improves survival and perhaps even the quality of life. Gemcitabine is active and well tolerated as well. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared to single agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single agent chemotherapy should remain the standard treatment. The two main research-lines to be explored in the near future are the introduction of biological agents in the treatment schemes and the development of specifically designed schedules of cisplatin-based regimens. However, practicing a multidimensional geriatric awsessment for individualized treatment choice in NSCLC elderly patients is mandatory.     

Paclitaxel: a hope for advanced non-small cell lung cancer?

Recent studies have shown that paclitaxel (Taxol); Bristol-Myers Squibb Co., Princeton, NJ) is an active agent in the treatment of advanced non-small cell lung cancer (NSCLC). Early trials in patients with advanced NSCLC utilised a 24 h infusion schedule and reported objective tumour responses in 21 - 24% of patients. Shorter infusion schedules have equivalent efficacy, and combined results from 14 separate trials of single agent paclitaxel in advanced NSCLC show an overall tumour response rate of 26%. Alternative schedules of paclitaxel from the traditional regimen every three weeks are under active investigation, but it is premature to assess whether these will yield improved efficacy for patients with advanced NSCLC. A single multicentre randomised trial of paclitaxel versus best supportive care in advanced NSCLC showed a significant survival advantage for the chemotherapy arm. Two large randomised Phase III trials have shown that paclitaxel and cisplatin is modestly more effective than cisplatin and podophyllotoxin combinations. The addition of cisplatin or carboplatin to paclitaxel results in higher response rates than for each of the drugs as single agents, but it is unclear whether the combinations yield superior survival or quality of life compared to single agent paclitaxel, or to other paclitaxel-containing regimens.     

Economic evaluation of gemcitabine alone and in combination with cisplatin in the treatment of nonsmall cell lung cancer

OBJECTIVE: To evaluate the cost effectiveness of gemcitabine in the treatment of nonsmall cell lung cancer (NSCLC). METHODS: Gemcitabine was compared with best supportive care and gemcitabine/cisplatin was compared with three standard chemotherapies and four other novel chemotherapy combinations. Costs and effectiveness measures were based on resource and outcome data from previously reported clinical trials. All direct costs associated with NSCLC treatment were included and adjusted to year 2000 values. PERSPECTIVE: UK National Health Service. RESULTS: Gemcitabine plus best supportive care was associated with an incremental cost per progression-free life year gained of pound sterling5228 compared with best supportive care alone. In comparison with standard chemotherapies, gemcitabine/cisplatin was associated with an incremental cost per progression-free life year gained of pound sterling1751 versus etoposide/cisplatin and cost per 1-year survival gain of pound sterling5681 versus mitomycin/vinblastine/platinum. Incremental cost per tumour response was pound sterling2032 relative to etoposide/cisplatin, pound sterling5169 relative to mitomycin/ifosfamide/cisplatin and pound sterling6240 relative to mitomycin/vinblastine/platinum. Compared with four novel (newer) combination chemotherapies gemcitabine/ cisplatin showed cost savings in each case, with the same or better outcome. Thus, gemcitabine/cisplatin showed improved cost effectiveness and dominance. Sensitivity analyses showed the results were robust to variations to the values of key parameters. CONCLUSION: Gemcitabine alone or in combination with cisplatin was assessed to be a cost-effective or cost-saving therapy when compared with best supportive care, standard chemotherapy regimens and novel chemotherapy combinations. Chemotherapy regimens containing gemcitabine therefore represent good value for money and efficient use of healthcare resources in the treatment of advanced NSCLC.     

Cost utility of chemotherapy and best supportive care in non-small cell lung cancer

Polychemotherapy is the therapeutic option recommended for nonresectable, non-small cell lung cancer (NSCLC). However, the modest gains in survival, and the frequent and often serious adverse effects, associated with chemotherapy should also be considered when deciding on therapy. We therefore performed a cost-utility analysis of chemotherapy and best supportive care in NSCLC. Effectiveness and costs were analysed on 70 patients who were randomised to receive one of 3 treatments: VP (vindesine and cisplatin), CAP (cyclophosphamide, doxorubicin and cisplatin), or best supportive care. Subsequently, an assessment of the value of polychemotherapy and best supportive care was performed by oncology personnel using the time trade-off technique. Polychemotherapy was found to be more effective than best supportive care, but was also more costly and had a lower value score. Because of its cost utility and its higher value, best supportive care should not be discarded as an alternative for the treatment of NSCLC.     

A review on the treatment of relapsed/metastatic head and neck cancer

The efficacy of traditional chemotherapy in inducing objective responses and prolonging survival in recurrent or metastatic head and neck cancer has been disappointing. More recent drugs have not proven superior to the classic regimen of cisplatin and 5-fluorouracil. Anti-EGFR monoclonal antibodies, either as single agents or associated to chemotherapy, have been shown to be active and little toxic. Among them, cetuximab has proven to be the most promising. Indeed the Extreme study, which compared the classic couple cisplatin (CDDP) + 5-fluorouracil with the same regimen plus cetuximab, has constituted a remarkable innovation. The results of that trial seem to indicate a third agent added to CDDP and 5-fluorouracil improved both progression-free survival and overall survival in the recurrent or metastatic setting. Unfortunately, the results obtained with the tyrosine kinase inhibitors are less impressive, and additional studies are needed to explore the potentiality of this class of drug. As far as antiangiogenetics are concerned, the research is insufficient for any conclusion to be drawn in terms of efficacy. It is hoped that, in the near future, the most active combination between biological agents and traditional chemotherapy will be found, so that the path successfully taken in other neoplastic diseases may be retraced.     

Pharmacotherapy for oesophagogastric cancer

Gastric cancer is the seventh and oesophageal cancer the ninth most common cancer in the UK, and >50% of patients present with locally advanced or metastatic disease. The incidence of oesophageal and oesophagogastric junctional tumours is increasing, making these important disease entities to understand and research. Despite improvements in surgical and peri-operative supportive care, 3-year overall survival with surgery alone for resectable disease is still poor. Outcomes in localised oesophageal cancer are improved with pre-operative chemotherapy, and in gastric cancer with peri-operative treatment or post-operative chemoradiotherapy. Oesophageal squamous cell carcinoma can be treated with definitive chemoradiotherapy as an alternative to surgery. While survival in patients presenting with metastatic disease is improved with the addition of systemic chemotherapy, median survival remains <1 year. Patients who are otherwise fit can be offered chemotherapy and this is superior to best supportive care. Regimens including a platinum and an anthracycline agent are favoured by the results of randomised trials. No standard second-line therapy has emerged. New research into taxanes has shown promising anti-cancer activity, and novel areas of investigation include incorporation of agents targeting vascular endothelial growth factor or epidermal growth factor receptor into standard regimens. This review focuses on the clinical trial evidence that dictates the optimal management of localised and advanced oesophagogastric cancer, focusing on pharmacotherapy. We examine areas of current research and highlight future therapeutic directions.     

Vinorelbine: a review of its use in elderly patients with advanced non-small cell lung cancer

Vinorelbine is a semisynthetic vinca alkaloid that is effective as monotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC). In the large comparative Elderly Lung Cancer Vinorelbine Italian Study (ELVIS), patients receiving vinorelbine monotherapy achieved an objective response rate of 19.7%. The median survival time and the 1-year survival rate were significantly higher in recipients of vinorelbine plus best supportive care than in recipients of best supportive care alone. Vinorelbine recipients generally scored better than recipients of best supportive care on quality-of-life (QOL) functioning scales and experienced significantly fewer lung cancer-related symptoms; however, QOL scores were worse with vinorelbine for parameters relating to drug tolerability. Comparative phase III trials investigating the efficacy of combination therapy with vinorelbine and other agents specifically in elderly patients with advanced NSCLC have been conducted only for the combination of vinorelbine and gemcitabine [the Southern Italy Cooperative Oncology Group (SICOG) trial and the Multicenter Italian Lung Cancer in the Elderly Study (MILES)]. Objective response rates for vinorelbine/gemcitabine combination therapy in these phase III trials were 22 and 20%, respectively. The SICOG trial was closed early when an interim analysis demonstrated a significant survival advantage for combination therapy with vinorelbine plus gemcitabine over vinorelbine monotherapy. However, a survival advantage for combination therapy versus vinorelbine monotherapy was not demonstrated in the larger MILES trial. The main adverse effect of vinorelbine monotherapy in the elderly is myelosuppression. Adverse events associated with most antineoplastic agents, such as mild alopecia, nausea, vomiting and mucositis, were reported in clinical trials; however, these events were rarely severe. Mild-to-moderate neurotoxicity, including constipation (presumably from autonomic neuropathy), was also reported. The addition of gemcitabine to vinorelbine increased the incidence of both haematological and nonhaematological adverse events. However, there was no significant increase in the incidence of life-threatening toxicity. Vinorelbine as a single agent is effective in elderly patients with NSCLC and is associated with improved survival and at least a trend towards improved QOL parameters compared with best supportive care alone. Vinorelbine was associated with a generally manageable tolerability profile. The benefit of adding gemcitabine to vinorelbine for the treatment of NSCLC in the elderly is equivocal; improved survival was reported in one comparative trial, but not in another larger one. Vinorelbine is an effective and well tolerated palliative treatment option for elderly patients with advanced NSCLC.     

The current status of docetaxel for advanced non-small cell lung cancer

Docetaxel is an active single agent in both first- and second-line therapy of patients with advanced non-small cell lung cancer (NSCLC). Randomized trials versus best supportive care have documented an improvement in overall survival for docetaxel therapy in both settings. Docetaxel also produced a significant 1-year survival rate improvement when compared with vinorelbine or ifosfamide as second-line therapy. Docetaxel has been extensively investigated in phase I/II studies in combination with cisplatin, carboplatin, irinotecan and gemcitabine. Substantial activity has been demonstrated. In a randomized phase II trial comparing docetaxel plus cisplatin with docetaxel plus gemcitabine, the efficacy of the two regimens was almost identical (response rates 32 and 34%; 1-year survival rates 42 and 38%). However, the combination of docetaxel with gemcitabine was associated with significantly less grade III/IV neutropenia, diarrhea and nausea/vomiting. Three drug regimens combining docetaxel with, for example, gemcitabine and carboplatin or with ifosfamide and cisplatin, are producing very high response rates in phase II trials. Whether three-drug combinations including docetaxel will result in an improved outcome for patients with advanced NSCLC remains to be determined.     

Management options for malignant pleural mesothelioma: clinical and cost considerations

Malignant pleural mesothelioma (MPM) is a resistant form of lung cancer that is often related to prior asbestos exposure. While surgical resection and radiotherapy techniques have been refined in recent years, neither has been proven to significantly extend patient survival compared with untreated controls. Until the release of pemetrexed in 2004, even combination chemotherapy regimens often resulted in a response rate of <20%. A recent phase III trial documented a 41.3% response rate for cisplatin plus pemetrexed. In the future, new multimodality regimens featuring novel targeted therapies directed against molecular targets, such as the vascular endothelial growth factor, hold the greatest promise for improved outcomes in MPM. The standard radiographic assessment of response to MPM therapy remains a poor surrogate for clinically relevant endpoints such as median survival. Furthermore, it is not currently known whether aggressive multimodality treatment for MPM will improve survival or quality of life above and beyond symptomatic care. Ongoing clinical trials are comparing chemotherapy and surgery with supportive care in an effort to define the role of different therapies in MPM. MPM treatment is a costly public health issue; after efficacy is proven, additional studies are needed to measure the cost effectiveness of MPM treatment regimens.     

The chemotherapy of head and neck cancer

Studies of combination therapy [with agents such as cisplatin, 5-fluorouracil (5-FU) and methotrexate] have shown some improvements in response rate; however, no obvious survival advantage over monotherapy in the treatment of patients with metastatic or advanced locoregional cancer of the head and neck have been observed. In the neoadjuvant setting, chemotherapy is helpful in preserving the larynx and hypopharynx but has no proven impact (positive or negative) on survival. New treatment options are needed to improve survival in head and neck cancer. Among the new options for chemotherapy in metastatic/recurrent disease is docetaxel. With monotherapy, response rates of 23-42% are seen, and, when used in combination with cisplatin and 5-FU, response rates of 52-100% have been reported in phase I/II trials. A phase III trial of the addition of docetaxel to standard neoadjuvant therapy with cisplatin and 5-FU is now underway.     

Esophagogastric cancer: integration of targeted therapies into systemic chemotherapy

Although combination chemotherapy has been shown to be more effective than single agents in advanced esophagogastric cancer, the better response rates have not fulfilled their promise as overall survival times from best combination still range between 8 to 11 months. So far, the development of targeted therapies stays somewhat behind their integration into treatment concepts compared to other gastrointestinal diseases. Thus, the review summarizes the recent advances in the development of targeted therapies in advanced esophagogastric cancer. The majority of agents tested were angiogenesis inhibitors or agents targeting the epidermal growth factor receptors EGFR1 and HER2. For trastuzumab and bevacizumab, phase III trial results have been presented recently. While addition of trastuzumab to cisplatin/5-fluoropyrimidine-based chemotherapy results in a clinically relevant and statistically significant survival benefit in HER 2+ patients, the benefit of the addition of bevacizumab to chemotherapy was not significant. Thus, all patients with metastatic disease should be tested for HER-2 status in the tumor. Trastuzumab in combination with cisplatin/5-fluoropyrimidine-based chemotherapy is the new standard of care for patients with HER2-positive advanced gastric cancer.     

老年非小细胞肺癌患者化疗药物治疗进展

结合国内外相关文献资料分析老年非小细胞肺癌(NSCLC)患者化疗的必要性,第三代抗肿瘤药物和不同化疗方案的疗效,以及分子靶向药物在老年患者中的治疗进展情况.单药化疗仍然是老年晚期NSCLC 一线治疗方案;部分PS 评分佳的老年患者可采用含卡铂、低剂量顺铂联合方案化疗;分子靶向药物治疗因其口服方便及不良反应小,适用于高龄、PS 评分差或有明显合并症的老年晚期NSCLC 患者的一线治疗.化疗对老年晚期NSCLC 患者疗效好,单药化疗、含铂或不含铂联合化疗及靶向治疗疗效相似.     

Lung cancer: a review.

The frequency, risk factors, pathophysiology, diagnosis, and management of lung cancer are reviewed. An estimated 157,400 Americans died of lung cancer in 2001. Lung cancer is the second most frequent cancer in both men and women. The major risk factor for lung cancer is smoking, which accounts for 75-80% of lung cancer-related deaths. Lung cancers can be broadly classified into two forms, small-cell carcinomas and non-small-cell carcinomas. Non-small-cell lung cancer is more common, accounting for up to 75% of lung cancers. Lung cancer is diagnosed by chest radiography, sputum cytology, bronchoscopy, needle biopsy, and other techniques. Surgery plays a major role in managing stage I and stage II non-small-cell lung cancer and may be used for stage III disease. Patients with stage IIIa disease may be surgical candidates, but involvement of mediastinal lymph nodes reduces the probability of survival. Adjuvant irradiation may reduce the rate of local recurrence but does not increase survival time. Adjuvant chemotherapy may confer a small survival-time advantage if the regimen includes cisplatin. Chemotherapy combined with radiation therapy may produce a survival advantage over irradiation alone. Patients with advanced non-small-cell lung cancer should receive combination chemotherapy. Several regimens have shown a survival advantage over best supportive care. Paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan have activity both as single agents and in combination. Surgery has only a limited role in the management of small-cell lung cancer. Patients with limited disease should receive a platinum-based chemotherapy regimen plus radiation therapy. Combination chemotherapy should be offered to patients with extensive disease. The most active regimens contain cisplatin or carboplatin. Paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan combinations have shown some promise. Lung cancer, although highly preventable, is usually diagnosed at an incurable stage. Chemotherapy is playing an increasingly important role alongside surgery and radiation therapy in the management of this disease.     

Cytotoxic chemotherapy for pancreatic cancer: Advances to date and future directions

Chemotherapy remains the mainstay of treatment for pancreatic cancer as most patients present with advanced disease, which precludes locoregional treatment. However, the efficacy of chemotherapy is limited. Gemcitabine is the only agent that improves symptoms and confers a modest survival advantage. Many combination therapy regimens have been studied in phase II settings. Eleven randomised phase III trials have been conducted to compare gemcitabine-containing regimens with gemcitabine monotherapy since gemcitabine became available clinically. The combination of gemcitabine plus capecitabine has demonstrated a survival advantage over gemcitabine, whereas gemcitabine plus oxaliplatin and gemcitabine plus cisplatin have shown improved progression-free survival or time to tumour progression but failed to demonstrate a survival advantage over gemcitabine. The search for effective therapy for advanced pancreatic cancer continues. Gemcitabine in combination with cytotoxic agents or molecular targeted agents hold promise.     

Emerging drugs in endometrial cancers

Importance of the field: Endometrial cancer remains the most common gynecologic malignancy. The treatment of endometrial cancer is rapidly evolving.

Areas covered in this review: In this article, we aim to review current and future treatment options in the medical treatment of endometrial cancers.

What the reader will gain: The cornerstone of curative therapy for patients with endometrial cancer is surgical treatment. Cytotoxic chemotherapy is the mainstay of therapy for metastatic and advanced endometrial cancer. The most active chemotherapy agents are anthracyclines, platinum compounds and taxanes. Combination chemotherapy has produced higher response rates than single agent therapy. Cisplatin and doxorubicin combination chemotherapy has served as the control arm in many trials. Three-drug combination regimen has shown the highest response rate but with increased toxicity. Despite the lack of published data supporting the superiority of the paclitaxel plus carboplatin combination over doxorubicin and cisplatin, many centers prefer this regimen as a standard of care. Hormonal therapy should be considered in patients with low grade tumors and in those with a poor performance status. Recent advances in the understanding of the molecular biology of endometrial cancer have led to development of targeted therapies. Among these the more promising ones are mTOR inhibitors and antiangiogenic agents.

Take home message: Clinical trials are planned to further explore how to best incorporate novel agents into the current treatment algorithm with the aim to improve outcome for women with endometrial adenocarcinomas.     

Complete estrogen blockade for the treatment of metastatic and early stage breast cancer

Complete estrogen blockade has long been sought as a more effective means of controlling breast cancer compared with single agent endocrine therapy. This approach may be accomplished through the use of agents which reduce estrogen production combined with agents that prevent the activity of estrogen at the cellular level. For prostate cancer, another hormonally responsive malignancy, this approach has not been successful at improving survival compared with that achieved with single agent therapy. Preclinical information is contradictory for many promising combinations and may not reflect the true nature of in vivo interaction between agents. For premenopausal patients with metastatic breast cancer, the combination of a luteinising hormone-releasing hormone (LHRH) agonist and tamoxifen is clearly effective, but whether the combination is more effective than either single agent is still controversial. Similar response rates and overall survival were reported with goserelin or goserelin plus tamoxifen by Jonat et al. in 1 randomised, prospective study, but the addition of tamoxifen improved time to progression. A second trial comparing buserelin plus tamoxifen with either single agent reported superior efficacy in terms of response rates, disease-free survival and overall survival with combination therapy. A meta-analysis of 4 randomised trials making similar comparisons, demonstrated significant improvement in median overall survival, progression-free survival, response rate, and duration of response with the combination of a LHRH agonist (goserelin or buserelin) and tamoxifen in premenopausal breast cancer patients with metastatic disease. For postmenopausal women with metastatic breast cancer, the addition of an aromatase inhibitor to tamoxifen has yet to be prospectively compared to single agent therapy. Use of endocrine combinations in the treatment of early stage breast cancer is under investigation. Preliminary results of some of the ongoing adjuvant therapy trials indicate that the combination of a LHRH agonist and tamoxifen may have similar efficacy to cyclophosphamide, methotrexate, and fluorouracil chemotherapy in premenopausal women with estrogen receptor-positive tumour. Addition of LHRH agonist therapy in premenopausal patients with estrogen receptor-positive tumour who had maintained the ovarian function following chemotherapy [cyclophosphamide, doxorubicin (adriamycin), fluorouracil, and tamoxifen], also led to a reduction in the risk of recurrence. These studies have identified a sub-population of patients who may benefit from the addition of combination endocrine therapy. Overall, the issue is quite complex and the data from many ongoing trials are still awaited with anticipation to further delineate the role of complete estrogen deprivation in this disease.     

Drug therapy for gynaecological cancer in older women

A substantial proportion of all women dying from gynaecological malignancies are aged >75 years. Many reports have indicated that the survival of these patients is decreased compared with younger patients. Differences in biological behaviour, stage of the disease at presentation, and reluctance to undergo aggressive treatment with its associated morbidity are among the factors thought to be responsible for this difference in outcomes. However, investigations also indicate that elderly patients may receive less surgical and chemotherapeutic treatment without obvious clinical rationale. This overview is aimed at providing a guideline of chemotherapy appropriate for patients with epithelial ovarian, uterine (corpus and cervix), and vulvar cancer, aged 70 to 75 years and over. Platinum-based chemotherapy is the cornerstone of drug treatment in patients with ovarian cancer. Patients aged between 70 and 75 years with a good performance status can be treated with cisplatin- or carboplatin-based chemotherapy. Carboplatin, either in combination or as a single-agent, may offer advantages in patients aged >75 years and in those with a poor performance status. For patients with early recurrence there is no standard treatment, but several cytostatic and hormonal agents can be used with palliative intent. Patients with a late recurrence are probably best retreated with a platinum-based regimen. In metastatic endometrial cancer, hormonal therapy is the first choice in tumours expressing a progesterone receptor. Poorly differentiated tumours infrequently respond to endocrine therapy. In this situation, and for patients with tumours that have become resistant to hormonal manipulation, platinum-based chemotherapy may be used. The use of carboplatin-based regimens seems preferable in elderly patients, particularly in those with a decreased performance status. The usefulness of chemotherapy in elderly patients with cervical cancer is limited. In case of recurrent or metastatic disease, the use of single agent (low-dose) cisplatin should be balanced against best supportive care. Although overall chemoradiation seems superior than radiotherapy alone in patients with locally advanced cervical cancer, the feasibility of this approach in elderly patients needs further investigation. Chemoradiation might also be considered in patients with locally advanced vulvar cancer. However, treatment-related morbidity can be considerable and randomised studies are lacking to prove a survival benefit. Our understanding of the tolerance and effectiveness of chemotherapy in elderly patients is still incomplete due to a paucity of trials that specifically focus on this subset of patients. However, there appears no argument to withhold chemotherapy based purely on age.     

Silybum marianum (milk thistle) in the management and prevention of hepatotoxicity in a patient undergoing reinduction therapy for acute myelogenous leukemia

Hepatotoxicity has been observed with several chemotherapy agents and combination regimens. Conventional treatment methods often include supportive care or observation. We report a case of a patient with noted transaminitis presumed secondary to chemotherapy, which did not resolve with supportive care but was shown to respond to milk thistle. The patient had an immediate decrease in liver function tests and showed decreased elevation in levels upon treatment with subsequent chemotherapy regimens. This case demonstrates the potential efficacy of milk thistle as a unique hepatoprotective agent.