Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

BACKGROUND: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. METHODS: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). RESULTS: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. CONCLUSIONS: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.     

Adjuvant chemotherapy for surgically resected non-small cell lung cancer

Despite surgical resection, patients with early-stage (I to IIIA) non-small cell lung cancer (NSCLC) are at considerable risk of recurrence and death from their lung cancer. In recent years, multiple, large, randomized trials assessing the efficacy of adjuvant chemotherapy for resected NSCLC have been reported. Three of 6 trials with 300 or more patients with early-stage NSCLC have demonstrated that adjuvant cisplatin-based chemotherapy can significantly improve 5-year survival in carefully selected patients with resected NSCLC. These benefits have been confirmed in a meta-analysis of modern cisplatin-based adjuvant trials. The most consistent benefit has been reported in patients with resected stage II and IIIA NSCLC. The benefit of adjuvant chemotherapy in patients with resected stage IB NSCLC is less concrete. Herein, we review the results of the major adjuvant chemotherapy trials and their implications for the treatment of patients with completely resected NSCLC. A future challenge will be to identify the subsets of patients who will derive the greatest benefit from adjuvant chemotherapy. Current trials are also underway to define the role of novel targeted therapies, such as inhibitors of the epidermal growth factor receptor and monoclonal antibodies, in adjuvant treatment strategies.     

The present status of postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers, with patients having a poor prognosis. Approximately one third of NSCLC patients present with early-stage disease in which potentially curative resection and multi-modality therapy. Although adjuvant chemotherapy is the standard practice for patients with stages I-III breast and colorectal cancer, the therapeutic efficacy of adjuvant chemotherapy, following complete surgical resection of early stage NSCLC, has not been fully established. Several prospective randomized trials for patients with early stage NSCLC (stages I-IIIA) have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy, as demonstrated in the 1995 meta-analysis performed by the NSCLC Collaborative Group. Studies from Japan have reported that adjuvant therapy with uracil-tegaful (UFT) afforded an improvement of 4% in the 5-year survival rate and a relative risk reduction of 26% in mortality at 5 years among patients with T1-2N0 (stage I) disease. In particular, the Japan Lung Cancer Research Group has demonstrated an improvement in the 5-year survival rate of 11%, favoring chemotherapy with UFT in the subset of patients with T2N0 (stage IB) disease. Two published meta-analyses based on abstracts have estimated a relative risk reduction in mortality of 11-13% at 5 years. The Lung Adjuvant Cisplatin Evaluation (LACE), which was based on a pooled analysis of five randomized trials, has demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with completely resected NSCLC. This benefit depended on stage, being greatest in patients with stage II or IIIA disease. This analysis has suggested that platinum-based adjuvant chemotherapy may have no benefit for patients with stage IA and only a marginal benefit for patients with stage IB. Thus, the information available at the current time supports the administration of adjuvant chemotherapy for patients who have undergone complete resection of stages IB-IIIA NSCLC. Further research is needed to define the role of adjuvant platinum-based chemotherapy and its use, in conjunction with chest radiotherapy as the treatment for patients with resected stages IB and IIIA NSCLC.     

Results of induction chemotherapy followed by surgical resection in patients with stage IIIA (N2) non-small cell lung cancer: the importance of the nodal down-staging after chemotherapy

Objective: Chemotherapy of stage IIIA non-small cell lung cancer (NSCLC) using second generation, cisplatin-based combinations has shown to improve the results; however, the distant relapses remain the major problem. Encouraging results in the treatment of stage IV NSCLC with newer agents (gemcitabine, placlitaxel) has encouraged us to use them in stage III. The aim of this study was to assess feasibility and efficacy of induction chemotherapy with cisplatin and gemcitabine followed by surgery for patients with stage IIIA (N2) NSCLC. Methods: From February 1996 to December 1999, 36 consecutive patients with mediastinoscopically staged N2 NSCLC received three cycles of cisplatin (80 mg/m², day 2) and gemcitabine (1200 mg/m², day 1+8) followed by surgery in responding patients. Patients with stable disease or even local progression received radiotherapy. All patients had clinical N2 disease (mediastinal lymph nodes metastasis) observed on CT scan. Results: No major complications of the chemotherapy occurred. Twenty-five patients (70%) had a clinical partial response and were surgically explored, with 18 complete resections (70%). There were no in-hospital deaths, although four (16%) major complications: bronchopleural fistula (two), respiratory insufficiency (one), oesophagospleural fistula (one). In the total group of 36 patients, 3-year survival was 20%. So far, no patient without surgery has survived longer then 27 months; median survival was 8 months. In the group of the 25 patients who underwent surgery 3-year survival was 30%, with a median survival of 21 months. The difference is significant (P=0.0027). In the surgical group, the survival of patients with down staged disease (56%) was greater than that of patients with persistent N2 disease (44%) after chemotherapy (3-year survival of 59 and 0%, respectively; P=0.0013). Conclusion: induction chemotherapy with cisplatin and gemcitabine resulted in major tumour regression in a large percentage of patients with clinical N2 disease. In responding patients both the complete respectability rate and survival were higher when compared to historical controls. Survival was significantly better in patients down-staged to a mediastinal negative disease.     

Current status and future perspectives on chemotherapy in patients with gastric cancer: can the clinical data from Japan lead to a standard international therapy?]

From a meta-analysis of clinical studies in Japan and the West, although no survival benefit for stage I gastric cancer was observed in patients who received postoperative adjuvant chemotherapy, the survival benefit for patients with stage II and III disease was small and marginal effect, respectively, since the odds ratios were between 0.80 and 0.82 with a 95% confidence interval of less than 1.0. Anticancer drugs used for combination therapy included mitomycin C, anthracyclines, alkylating agents, and 5-fluorouracil. Increased long-term survival and the prevention of peritoneal recurrence were found in some patients who received combination therapy with mitomycin C, 5-fluorouracil, and nonspecific immunomodulators such as PSK and OK-432. Regarding chemotherapy for advanced and recurrent cases, administration of biochemical modulators such as low-dose FP and the new dehydropyrimidine dehydrogenase inhibitory fluoropyrimidine agent S 1 resulted in increased response rates, improved quality of life, and prolongation of survival. The development of rigorous trials and personalized chemotherapy with molecular targeting are needed to achieve further survival benefit for patients with gastric cancer.     

Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials

BACKGROUND: Surgery is considered the treatment of choice for patients with resectable stage I and II (and some patients with stage IIIA) non-small cell lung cancer (NSCLC), but there have been no previously published systematic reviews. METHODS: A systematic review and meta-analysis of randomised controlled trials was conducted to determine whether surgical resection improves disease specific mortality in patients with stages I-IIIA NSCLC compared with non-surgical treatment, and to compare the efficacy of different surgical approaches. RESULTS: Eleven trials were included. No studies had untreated control groups. In a pooled analysis of three trials, 4 year survival was superior in patients undergoing resection with stage I-IIIA NSCLC who had complete mediastinal lymph node dissection compared with lymph node sampling (hazard ratio estimated at 0.78 (95% CI 0.65 to 0.93)). Another trial reported an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small study reported a survival advantage among patients with stage IIIA NSCLC treated with chemotherapy followed by surgery compared with chemotherapy followed by radiotherapy. No other trials reported significant improvements in survival after surgery compared with non-surgical treatment. CONCLUSION: It is difficult to draw conclusions about the efficacy of surgery for locoregional NSCLC because of the small number of participants studied and methodological weaknesses of the trials. However, current evidence suggests that complete mediastinal lymph node dissection is associated with improved survival compared with node sampling in patients with stage I-IIIA NSCLC undergoing resection.     

Results of Surgical Treatment After Neoadjuvant Chemotherapy for Stage III Non-Small Cell Lung Cancer

BACKGROUND: The potential benefits of an approach combining neoadjuvant chemotherapy and surgery in stage IIIA and IIIB NSCLC have to be weighed against a potential increase in postoperative complications. We evaluated the results in terms of postoperative complications and survival in patients with stage III NSCLC who underwent complete surgical treatment after neoadjuvant chemotherapy with two regimens: mitomycin, vinblastine, and cisplatin (MPV) versus gemcitabine and cisplatin (GC). METHODS: From March 1991 to September 2005, 110 patients with stage III NSCLC (86 stage IIIA and 24 stage IIIB) underwent complete surgical treatment after neoadjuvant chemotherapy. Ninety-two patients were men and 18 were women, with a mean age of 59 (range, 39-80) years. The neoadjuvant chemotherapy regimen was MPV in 72 patients and GC in 38. RESULTS: The overall response (>50%) to chemotherapy was 84%. Postoperative mortality and morbidity were 1.8% and 20%, respectively. Overall 5-year survival was 46%. Minor response to neoadjuvant chemotherapy (<50%) and residual nodal N2 involvement in stage IIIA had an adverse impact on survival (p < 0.05). CONCLUSIONS: Favorable long-term survival was observed after neoadjuvant chemotherapy with MPV and GC regimens in stage IIIA and IIIB NSCLC, with relatively low postoperative mortality and morbidity. Caution should be taken when offering surgical treatment to patients with minor response to induction chemotherapy and residual N2 disease in view of the significantly reduced survival.     

Adjuvant Chemotherapy for Invasive Bladder Cancer: A 2013 Updated Systematic Review and Meta-Analysis of Randomized Trials

Context

The role of adjuvant chemotherapy remains poorly defined for the management of muscle-invasive bladder cancer (MIBC). The last meta-analysis evaluating adjuvant chemotherapy, conducted in 2005, had limited power to fully support its use.

Objective

To update the current evidence of the benefit of postoperative adjuvant cisplatin-based chemotherapy compared with control (ie, surgery alone) in patients with MIBC.

Evidence acquisition

A comprehensive literature review was performed to identify all randomized controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy with control for patients with MIBC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to May 2013. An updated systematic review and meta-analysis was performed.

Evidence synthesis

A total of 945 patients included in nine RCTs (five previously analyzed, one updated, and three new) were examined. For overall survival, the pooled hazard ratio (HR) across all nine trials was 0.77 (95% confidence interval [CI], 0.59–0.99; p = 0.049). For disease-free survival, the pooled HR across seven trials reporting this outcome was 0.66 (95% CI, 0.45–0.91; p = 0.014). This disease-free survival benefit was more apparent among those with positive nodal involvement (p = 0.010).

Conclusions

This updated and improved meta-analysis of randomized trials provides further evidence of an overall survival and disease-free survival benefit in patients with MIBC receiving adjuvant cisplatin-based chemotherapy after radical cystectomy.     

Postoperative adjuvant chemotherapy for stage I non-small cell lung cancer

Objective: Surgery constitutes the mainstay of treatment in stage I non-small cell lung cancer (NSCLC). However, a significant fraction of patients after surgical resection die mainly due to systemic relapse. Nonetheless, the best adjuvant treatment to improve survival and decrease relapse rate remains as an ever controversial issue. Therefore, we conducted a randomized trial to determine whether postoperative adjuvant chemotherapy is beneficial in prolonging survival and decreasing recurrence in patients with completely resected stage I NSCLC. Methods: It was designed as a randomized, prospective two-armed study with surgery only (control group, 59 patients) versus surgery plus adjuvant MVP (mitomycin C, vinblastin and cisplatin) chemotherapy (study group, 59 patients). Results: Data for all the patients were complete. Twenty-four patients in the control group and nine patients in the study group experienced tumor recurrence during the follow-up. Neither histological type nor surgical extent correlated with recurrence. However, the addition of adjuvant MVP chemotherapy could decrease the rate of recurrence and the incidence of cancer-related death after surgery in the patients of stage I NSCLC (P<0.05). We followed up at least 5 years, and the duration of mean follow-up was 7.3 years. The rates of the loco-regional and distant metastases were 3.4 and 40.7% in the control group, and 3.4 and 11.9% in the study group, respectively. The 5- and 10-year survival rates were 74.6 and 56.3% in the control group, and 81.4 and 65.0% in the study group, respectively (P=0.19, log-rank test). The 5- and 10-year disease-free survival rates were 64.8 and 54.8% in the control group, and 88.8 and 76.8% in the study group, respectively (P=0.002, log-rank test). Conclusions: Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the incidence of distant metastasis and prolong the disease-free survival of the patients with stage I NSCLC after surgery.     

Long-term survival of resectable subset after induction chemotherapy in patients with locally advanced head and neck cancer

BACKGROUND: Although meta-analysis showed that survival improved with concurrent chemoradiation in locally advanced head and neck cancer, neoadjuvant chemotherapy is still unique, because it renders curative surgery feasible for marginally resectable head and neck cancer patients. METHODS: We reviewed patients with locally advanced head and neck cancer, who had been treated with neoadjuvant chemotherapy between June 1984 and February 2001 at the Seoul National University Hospital. RESULTS: A total of 167 patients were included. After 2 to 3 chemotherapy cycles, either surgery (38 patients) or radiation (104 patients) was conducted. Those who received surgery exhibited better survival than those who received radiation [median survival: not reached vs 33.6 months (95% CI: 22.6-44.7), p = .006]. The 5-year and 10-year survival rates of surgery group were 63.2% and 59.8%. CONCLUSION: The potential benefit of neoadjuvant chemotherapy with surgery in patients with locally advanced head and neck cancers merits further evaluation in future clinical trials.     

Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC

Objective: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III N2 non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. Methods: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44 Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. Results: Group I and II comprised T1/2 tumors in 47 and 28%, T3 tumors in 45 and 41%, and T4 tumors in 8 and 31% of the patients, respectively (P=0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (P=0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (P=0.6), a R0-resection rate of 92 and 94% (P=0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P<0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1–3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (P=0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. Conclusions: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of T4 tumors were admitted to radiochemotherapy.     

A phase II study of mitomycin,fluorouracil, folinic acid,and irinotecan (MFI) for the treatment of transitional cell carcinoma of the bladder

Background and objectivesCisplatin-based chemotherapy is standard care for metastatic transitional cell carcinoma (TCC) of the urinary tract. However it is not appropriate for all patients, particularly those with poor renal function. There is no clear consensus on the optimal regimen for these individuals or for those after cisplatin failure. Here we present data using mitomycin, 5-fluorouracil, and irinotecan (MFI) in these patients.Materials and methodsPatients with TCC, who had either received cisplatin-based chemotherapy previously or who were not deemed fit for cisplatin therapy (creatinine clearance was less than 60 ml/min) were eligible for treatment with the experimental combination chemotherapy regimen MFI.ResultsThirty-six patients were treated with MFI between 2001 and 2004. Overall response rate was 19% and median overall survival (OS) was 5.4 months (95% CI 3.3–8.4 months). The response rate and overall survival in both groups was 19% and 5.4 months, respectively, (95% CI 2.9–7.1 months) in the pretreated and 2.5– 9.3 months in the untreated. The most common toxicity was malaise (grade 3 or 4 = 28%).ConclusionsMFI appear to be a combination which requires further investigation in patients where cisplatin and gemcitabine are not applicable.     

Early debulking surgery after chemotherapy in advanced cancer of the ovary

The main prognostic factor in advanced ovarian cancer is the volume of residual disease after the initial laparotomy. Early debulking surgery after several cycles of chemotherapy, before the emergence of resistant cell lines, could improve the prognosis of patients with bulky residual disease. This study concerns patients with advanced ovarian cancer entered into three prospective trials including IV cisplatin and anthracycline-based chemotherapy, early debulking surgery after three cycles of chemotherapy in case of initial residual disease superior 2 cm and intraperitoneal consolidation chemotherapy. Among 160 patients with stage III or IV, 80 (50%) had at least a residual tumor of more than 2 cm in diameter. Early debulking surgery was effectively performed in 54 patients (67.5%), leaving 39 patients with no residue over 2 cm. Twenty-one patients had no macroscopic residual disease. The median survival of all patients with initial residual disease over 2 cm was 23 months. Patients with no macroscopic residual disease at early debulking surgery had a median survival of 44 months. Early debulking surgery appears useful in advanced ovarian cancer with bulky residual disease. The objective of this operation is to achieve no macroscopic residual lesion.     

A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209)

OBJECTIVE: We performed a prospective randomized trial in patients with potentially resectable stage IIIA N2 non-small cell lung cancer to confirm the efficacy of induction chemotherapy before surgical resection. METHODS: Patients with stage IIIA N2 non-small cell lung cancer, all with histologically or cytologically confirmed metastases to the ipsilateral mediastinal lymph nodes, were randomly assigned to receive either three cycles of induction chemotherapy (cisplatin at 80 mg/m(2) on 1 day and vindesine at 3 mg/m(2) on 2 days) followed by surgery or surgery alone. RESULTS: This trial was prematurely terminated because the accrual rate was too slow, which lowered the study's statistical power considerably. From June 1993 through April 1998, a total of 62 patients were enrolled, and 31 patients were assigned to each treatment group. The objective clinical response rate of induction chemotherapy was 28%. Complete resection was achieved in 20 patients in the induction chemotherapy group (65%) and 24 in the surgery alone group (77%). Median follow-up was 6.2 years. Median overall survivals were 17 months for the induction group and 16 months for the surgery alone group. The estimated 1-, 3-, and 5-year survivals, respectively, were 68% (95% confidence interval 51%-85%), 23% (95% confidence interval 8%-38%), and 10% (95% confidence interval 0%-20%) for the induction chemotherapy group and 65% (95% confidence interval 48%-82%), 26% (95% confidence interval 11%-41%), and 22% (95% confidence interval 7%-37%) for the surgery alone group. There was no statistically significant difference in survival between the groups (P =.5274). Treatment-related death was not observed in either group. CONCLUSION: This randomized trial to compare induction chemotherapy (cisplatin and vindesine) followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer did not demonstrate a survival difference between the groups, although this may have been because the statistical power was limited.     

Preoperative chemotherapy for cStage III-pN0 patients with non-small cell lung cancer

Objectives: Survival benefits with preoperative chemotherapy for non-small cell lung cancer (NSCLC) remain controversial. Preoperative chemotherapy may act on micrometastasis but not lymph node metastasis. To clarify the role of induction chemotherapy for control of micrometastasis, we reviewed and compared 5-year follow-ups of clinical stage III but pathologically-proven node-negative NSCLC patients after complete resection with or without preoperative chemotherapy. Methods: We reviewed 148 consecutive patients who underwent anatomical lung resection and mediastinal nodal dissection for pathologically-proven node-negative NSCLC at our hospital between 1994 and 1999. Fifty-six patients were preoperatively diagnosed as stage III: 26 received platinum-based chemotherapy prior to surgery (PCT group) and 30 underwent surgery without any prior chemotherapy (PRS group). Results: The 5-year survival rate for clinical stage I/II and pathological node-negative patients was 74.9%; for clinical stage III, but for pathological node-negative patients it was 92.3% in the PCT and 63.3% in the PRS groups. The survival benefit of preoperative chemotherapy was significant for clinical stage III patients without node involvement. Conclusion: Preoperative chemotherapy may provide survival benefits for node-negative NSCLC patients.     

Efficacy of current adjuvant and neoadjuvant therapeutic concepts in gastric cancer?

The incidence of gastric cancer in Europe is declining but the prognosis after curatively intended surgery remains dismal. In recent years several studies and meta-analysis concerning the impact of adjuvant postoperative chemotherapy and chemoradiation as well as preoperative chemotherapy were published. This review aims to interpret results and to support decision making in individual patients. Results of trials on adjuvant chemotherapy were inconsistent and the studies were underpowered to detect meaningful but modest advantages. Meta-analyses including more than 3 000 patients revealed a significant survival benefit but no specific chemotherapy protocol can be regarded an optimal regimen. Postoperative adjuvant schedules including cisplatin led to high drop out rates due to toxicity. Applying cisplatin and infusional fluorouracil initially after diagnosis as a so called neoadjuvant therapy is better tolerated. Two trials testing this approach showed a significant survival benefit with preoperative cisplatin and infusional fluorouracil as compared to surgery alone. Postoperative chemoradiation was shown to be effective concerning local regional relapses and survival benefit in a large trial in the US but the majority of patients were treated with less radical lymph node dissection than it is routine in Germany. Enrollment of patients in prospective trials evaluating the impact of adjuvant and neoadjuvant strategies is warranted.     

Postoperative adjuvant therapy for stage IB non-small-cell lung cancer.

OBJECTIVE: Although surgical resection alone is considered adequate treatment in stage IB non-small-cell lung cancer (NSCLC), long-term survival is not satisfactory and the recurrence rate is quite high. The validity of postoperative chemotherapy at stage IB in terms of disease-free and overall survival was assessed in a randomised trial. METHODS: The trial was designed as a randomised, two-group study with postoperative adjuvant chemotherapy versus surgery alone as control group. All patients had stage IB disease (pT2N0) assessed after a radical surgical procedure. Chemotherapy consisted of treatment with cisplatin (100 mg/m(2) on day 1) and etoposide (120 mg/m(2) on days 1--3) for a total of six cycles. RESULTS: Between January 1988 and December 1994, 66 patients were included in the study. Thirty-three belonged to the adjuvant chemotherapy group and 33 to the control group. Groups were homogeneous for conventional risk factors. There was no clinical significant morbidity associated to chemotherapy. Patients were followed for a minimum period of 5 years. The rates of locoregional recurrence and distant metastases were 18 and 30%, respectively, in the adjuvant chemotherapy group and 24 and 43%, respectively, in the control group. The 5-year disease-free survival rates were 59% in the adjuvant group and 30% in the control group (P = 0.02). The difference in the Kaplan--Meier survival between the groups was significant as assessed using the log-rank test (P = 0.04). CONCLUSIONS: Our results suggest that adjuvant chemotherapy may reduce recurrences and prolong overall survival in patients at stage IB NSCLC deemed radically operated. Despite being difficult to accept, the use of adjuvant chemotherapy might have better long-term results.     

Chemotherapy for good-risk germ cell tumors: current concepts and controversies

Through a series of well-designed randomized clinical trials, the treatment of patients with cisplatin-based chemotherapy has evolved such that approximately 90% of patients who have good-risk metastatic germ cell tumor (GCT) will be cured of their disease. At present, first-line chemotherapy for patients who have good-risk metastatic GCT is three cycles of bleomycin/etoposide/cisplatin. An alternative to this is four cycles of etoposide/cisplatin. This article examines the progress that has been made in the development of chemotherapy for good-risk metastatic GCT and raises questions for further consideration and investigation.     

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC). METHODS: Thirty-seven patients with stage IV(A-B) NPC were treated with 3 cycles of cisplatin plus gemcitabine (cisplatin 80 mg/m(2) on day 1; gemcitabine 1250 mg/m(2) on days 1 and 8) 3-weekly as induction chemotherapy, followed by another 3 cycles of concurrent cisplatin (100 mg/m(2) on day 1) 3-weekly with accelerated radiotherapy (RT) at 70 Gy in 2-Gy fractions, 6 daily fractions per week. RESULTS: The overall response rate to induction chemotherapy was > 90%, and side effects other than uncomplicated hematologic toxicities were uncommon. All patients completed RT, with 92% receiving > or = 5 cycles of chemotherapy. At a median follow-up of 2.9 years, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 76% and 63%, respectively. CONCLUSIONS: Cisplatin plus gemcitabine is a well-tolerated, effective, and convenient induction chemotherapy regimen and warrants further studies to confirm its benefit in advanced NPC.     

Adjuvant chemotherapy for resectable non-small cell lung cancer (NSCLC)

A randomized clinical trial of adjuvant chemotherapy has been evaluated for non-small cell lung cancer (NSCLC) patients, because the prognosis of early NSCLC does not enough after surgery (stage I: 70-80%, stage II: 50% in overall 5-years survival). Japanese guide line for lung cancer treatment (2005 edition) recommends adjuvant chemotherapy after complete resection for pathological stage IB, II and IIIA. Previous studies have suggested that uracil-tegafur has benefit for stage IB NSCLC patients, and platinum-based adjuvant chemotherapy has benefit for stage IB, II and IIIA NSCLC patients. In 2007 ASCO Annual Meeting, Harpole D talked about molecular prognostic profiles in early resected NSCLC. The goal of this study design is to validate a molecular-based tumor model that identifies those patients at low risk for cancer recurrence who will not benefit from adjuvant chemotherapy. The remaining patients will be randomly assigned to observation (the present standard of care) or adjuvant chemotherapy to determine the efficacy of adjuvant in this population. Biomarker for response of chemotherapy will be available to know who has benefit from adjuvant chemotherapy. When each patient has appropriate adjuvant chemotherapy, the prognosis is improved by that.