Impact of histology on survival of resected non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy: subgroup analysis of the adjuvant vinorelbine (NVB) cisplatin (CDDP) versus observation in the ANITA trial

Background

Data issued from the survival outcome in the ANITA trial are reported according to histology in observation (n = 433) and adjuvant chemotherapy arms (n = 407).

Methods

In the ANITA trial, patients with resected stage IB, stage II and stage IIIA NSCLC were randomly assigned to vinorelbine plus cisplatin or to observation. In this retrospective analysis, Kaplan–Meier plots and life tables were used to describe survival within each treatment arm and each histological subgroup: observation adenocarcinoma, observation non-adenocarcinoma, chemotherapy adenocarcinoma, chemotherapy non-adenocarcinoma.

Results

In the observation arm, adenocarcinoma appears to be a poor prognostic factor in patients with resected NSCLC with a median survival of 37.3 months and 45.5 months for non-adenocarcinoma. In the treatment arm, adenocarcinoma may be a predictive factor of efficacy for adjuvant chemotherapy with a larger benefit from adjuvant vinorelbine-cisplatin chemotherapy, even though other histological subtypes also benefit from this treatment. The absolute benefit on survival at 5-years of chemotherapy was 13.9% in adenocarcinoma and 5.8% in non-adenocarcinoma.

Conclusion

Efficacy of vinorelbine-cisplatin in adjuvant setting is independent from histology. The poor outcome of adenocarcinoma found in the observation arm was reversed by the positive impact of chemotherapy, possibly due to a higher chemosensitivity of this subtype.     

Randomized controlled trial of neoadjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IIIA non-small cell lung cancer in China

Aim:   The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC).
Methods:   Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery.
Results:   The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm ( P  = 0.04 and P  = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm.
Conclusion:   Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC.     

A retrospective comparison of adjuvant chemotherapeutic regimens for non-small cell lung cancer (NSCLC): Paclitaxel plus carboplatin versus vinorelbine plus cisplatin

Background

Adjuvant chemotherapy with vinorelbine plus cisplatin (NP) has been demonstrated to increase overall survival in patients with stage II or IIIA non-small cell lung cancer (NSCLC). Although paclitaxel plus carboplatin (PC) failed to demonstrate efficacy in patients with stage IB NSCLC, an exploratory analysis suggested that patients with large tumors can benefit from adjuvant PC therapy.

Methods

Clinical outcomes of patients who received adjuvant NP or PC regimens after complete resection for their NSCLC were retrospectively compared.

Results

Of the 438 patients with completely resected NSCLC, 207 received PC and 231 patients received NP. The median relapse-free survival (RFS) was not significantly different, with 63.6 months for the PC group and 54.8 months for the NP group (P = .68). Overall survival also did not differ significantly between the two groups. The five-year overall survival rates were 73% (95% confidence interval (CI), 66–80%) in PC group and 71% (95% CI, 64–78%) in NP group (P = .71). In the subgroup analysis, RFS was comparable between the two groups across all variables. Analysis of the adverse events indicated that sensory neuropathy, alopecia, and myalgia are more frequent in the PC, while anemia, neutropenia, fatigue, anorexia, and vomiting are more common in the NP.

Conclusion

Although the adverse event profiles were different, the efficacy was comparable between the PC and NP regimens as adjuvant chemotherapy for NSCLC. While there is lack of prospective data, our retrospective data suggest that PC regimen can be considered as adjuvant chemotherapy for resected NSCLC.     

长春瑞滨联合顺铂治疗既往使用紫杉类的晚期非小细胞肺癌临床分析

目的　评价长春瑞滨联合顺铂治疗既往使用紫杉类的晚期非小细胞肺癌的疗效和毒性。方法　 3 0例既往紫杉类药物治疗过的ⅢB或Ⅳ期非小细胞肺癌患者 ,体能状况评分 (ECOG) 0～ 1分。 15例用NP方案 (长春瑞滨 +顺铂 )治疗 ,15例用MVP方案 (丝裂霉素 +长春地辛 +顺铂 )治疗。结果　NP组和MVP组有效率分别为 13 .3 %和 0 (P >0 .0 5)。NP组患者疾病进展时间较MVP组长(分别为 6个月和 3个月 ,P <0 .0 5) ,NP组中位生存时间较MVP组长 (分别为 9个月和 6个月 ,P <0 .0 5) ,NP组 1年生存率 (40 .0 % )明显高于对照组 (0 ,P <0 .0 5)。两组Ⅲ、Ⅳ度不良反应差异无显著性 (P >0 .0 5) ,患者可以耐受。结论　NP方案对既往使用紫杉类的、体能状况较好的晚期非小细胞肺癌患者有一定疗效 ,可使患者疾病进展推迟 ,中位生存期延长 ,1年生存率提高 ,且毒性可耐受     

Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy in Resected Advanced Non–Small-Cell Lung Cancer

IntroductionThis study was to assess the association of epidermal growth factor receptor (EGFR) mutation status and efficacy of adjuvant chemotherapy in patients with fully resected IIIA-N2 non–small-cell lung cancer (NSCLC).Materials and MethodsTumor samples (n = 150) from patients with IIIA-N2 NSCLC who either had or had not received paclitaxel plus carboplatin or vinorelbine plus carboplatin doublet adjuvant chemotherapy were analyzed for EGFR mutations. The association of the presence of EGFR mutations and survival was assessed.ResultsMutations were identified in 43 (28.7%) patients (n = 25 in the no chemotherapy [observation] arm and n = 18 in the chemotherapy arm). Patients with EGFR mutations had statistically significant improved disease-free survival (41 months [95% CI, 25.1-56.9 months] vs. 20 months [95% CI, 15.0-25.0 months]; 2P = .005) and overall survival (50 months [95% CI, 37.6-62.4 months] vs. 25 months [95% CI, 20.8-29.2 months]; 2P = .001), regardless of treatment. The patients with wild-type EGFR had greater overall survival with chemotherapy compared with no adjuvant therapy (hazard ratio [HR] 4.748 [95% CI, 2.844-7.928]; 2P < .001). In contrast, in patients with EGFR mutation in the observation group compared with the chemotherapy group had longer median disease-free survival (49 months [95% CI, 35.1-62.9 months] for the observation arm vs. 30 months [95% CI, 23.8-36.2 months] for the chemotherapy arm, 2P = .195) and overall survival (59 months [95% CI, 43.9-74.1 months] vs. 33 months [95% CI, 24.7-41.3 months]; 2P = .050).ConclusionsIn this exploratory study, the status of EGFR mutations was associated with different clinical outcomes in patients with resected IIIA-N2 NSCLC. Further studies are required to confirm that a patient's adjuvant treatment may be customized to their EGFR mutational status.     

Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study

PURPOSE: to evaluate the activity and toxicity of the combination cisplatin plus vinorelbine plus amifostine in advanced non small cell lung cancer (NSCLC). PATIENTS AND METHODS: a two-stage Simon design was applied. To proceed after the first stage, responses from seven of 19 patients were needed. Overall, 17 responses from 40 treated patients were required to comply with the design parameter. Inclusion criteria were cyto-histologically proven stage IIIB-IV NSCLC; age of 70 years or less; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; normal cardiac, hepatic, renal and bone marrow functions; and no previous chemotherapy. Patients were staged by physical examination, biochemistry, chest radiograph, brain, thoracic and abdominal computed tomographic (CT) scans, and bone scan. All patients received cisplatin 100 mg/m(2) intravenously (iv) day 1, vinorelbine 25 mg/m(2) iv days 1-8-15-22, amifostine 740 mg/m(2) iv day 1 every 4 weeks up to six cycles. Eleven of 40 enrolled patients were stage IIIB and 29 stage IV, with a median age of 57 years (range, 38-70 years). RESULTS: all patients were evaluable for response and toxicity (intention to treat analysis). We observed 20 (50%) objective responses, with four (10%) complete responses. Median time to progression was 20 weeks, and median survival was 45 weeks. The toxicity was manageable. The reported main toxicities were neutropenia grade 4 in 10% of patients, grade 1 and grade 3 nephrotoxicity both in 5% of patients and grade 1 amifostine-related hypotension in 15% of patients. CONCLUSION: these data show that cisplatin plus vinorelbine plus amifostine is an active and feaseable regimen in stage IIIB-IV NSCLC. A phase III trial comparing cisplatin plus vinorelbine versus cisplatin plus vinorelbine plus amifostine in advanced NSCLC is warranted.     

长春瑞宾联合顺铂或顺铂/丝裂霉素一线治疗不可手术非小细胞肺癌

目的比较长春瑞宾联合顺铂和丝裂霉素(MNP)和长春瑞宾联合顺铂(NP)一线治疗晚期非小细胞肺癌(NSCLC)的疗效与安全性.方法65例经细胞学或病理确诊的NSCLC患者分别接受MNP或NP方案化疗.长春瑞宾25 mg/m2静注,d18 c;顺铂为75 mg/m2,静脉滴注d1;MNP方案中丝裂霉素用法为6 mg/m2,静注第1天.两方案均每3周重复,两周期后评价疗效,并随访毒副反应.结果两组中位化疗周期数均为3.NP组PR为11例,总体有效率为33%;PD 5例(15%);MNP组PR为12例(38%),PD为5例(16%),与NP组相比,差异无显著性(P＞0.05).常见副反应有白细胞减少、贫血、便秘、恶心、呕吐等.MNP组Ⅲ与Ⅳ度白细胞减少症发生率高达41%;有3例因中性粒细胞减少并发感染而发热,其中1例死亡.NP与MNP组中位生存期分别为12与11个月,差异无统计学意义.结论长春瑞宾联合顺铂和丝裂霉素一线治疗晚期NSCLC在疗效上不优于长春瑞宾联合顺铂,毒副反应增加;不应作为晚期NSCLC的常规一线方案.     

Sequential chemotherapy with paclitaxel plus cisplatin, followed by vinorelbine, followed by gemcitabine in advanced non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 001)

Aim of this study was to determine the activity and toxicity of a sequential chemotherapy regimen in advanced non-small cell lung cancer (NSCLC). Fifty-one previously untreated stage IIIB/IV NSCLC patients were enrolled to receive two cycles of cisplatin plus paclitaxel (80/175 mg/m(2) every 21 days), followed by two cycles of vinorelbine (30 mg/m(2) on days 1 and 8 every 21 days), followed by two cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days). Forty-one patients (82%) completed the planned six cycles. Grade 3-4 neutropenia was the major toxicity (41% of patients) and it was mainly associated with vinorelbine administration. Response rate after cisplatin plus paclitaxel was 18%; this percentage increased to 41% after vinorelbine, and it reached 43% upon completion of the entire six cycle treatment program. Median survival time was 14.4 months, 1-year survival rate was 53%, and 2-year survival rate was 18%. Median time to disease progression was 6.8 months. This sequential chemotherapy regimen is feasible and active in patients with advanced NSCLC. This pilot experience provides the basis for an ongoing randomized phase III trial comparing our sequential regimen versus cisplatin plus gemcitabine.     

Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial

BACKGROUND: We aimed to compare the additional benefit of gemcitabine when combined with vinorelbine above that of standard vinorelbine treatment in patients with metastatic breast cancer. METHODS: In this phase III, multicentre, open-label, randomised study, 252 women with locally recurrent and metastatic breast cancer who had been pretreated with anthracyclines and taxanes were randomly assigned single-agent vinorelbine (30 mg/m(2), days 1 and 8) or gemcitabine plus vinorelbine (1200/30 mg/m(2), days 1 and 8). Both study treatments were administered intravenously every 21 days until disease progression, unacceptable toxic effects, or stoppage at the request of investigator or patient. The primary endpoint was median progression-free survival. Secondary objectives included assessments of response rate, disease duration, overall survival, and characterisation of the toxicity profiles of both regimens. This study is registered with ClinicalTrials.gov, number NCT00128310. FINDINGS: Between 2001 and 2005, 252 women were recruited and randomised for treatment. One of these patients was ineligible. Prognostic factors were well balanced between treatment groups (median number of metastatic sites in combination group 2 (range 0-5) and in vinorelbine group 2 (range 1-6); visceral disease in 76% and 75% of patients, respectively). Median progression-free survival was 6.0 months (95% CI 4.8-7.1) for patients given gemcitabine plus vinorelbine and 4.0 months (2.9-5.1) for those assigned vinorelbine; there was 1.9 months of difference (hazard ratio 0.66 [0.50-0.88]; p=0.0028). Overall survival was 15.9 months (12.6-19.1) for the gemcitabine plus vinorelbine group and 16.4 months (11.6-21.0) for the vinorelbine group; there was 0.5 months of difference (hazard ratio 1.04 [0.78-1.39]; p=0.8046). Objective response rates were 36% for patients assigned gemcitabine plus vinorelbine (n=45) and 26% for those assigned vinorelbine (n=33) (p=0.093). Grade 3 or 4 neutropenia was reported in 75 (61% [52-70]) of the participants assigned gemcitabine plus vinorelbine, compared with 55 (44% [35-53]) of those assigned vinorelbine alone (p=0.0074). Febrile neutropenia occurred in 13 (11%) of those assigned gemcitabine plus vinorelbine, and in seven (6%) of those assigned vinorelbine alone (p=0.15). Incidences of grade 3 or 4 non-haematological toxic effects were similar between the two treatment groups. INTERPRETATION: Patients with metastatic breast cancer assigned gemcitabine and vinorelbine had better progression-free survival compared with those assigned vinorelbine alone. However, this finding did not translate into a difference in overall survival. Although toxicity was manageable, patients in the combined group had more haematological toxic effects. These factors should be taken into account when deciding which chemotherapy patients should receive.     

Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group.

PURPOSE: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy. PATIENTS AND METHODS: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC). RESULTS: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL. CONCLUSION: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.     

Accelerated neoadjuvant chemotherapy of non-small cell lung cancer (NSCLC)

Thirty patients with marginally resectable stage IIIA or stage IIIB NSCLC were treated with cisplatin (80 mg/ m(2)/i.v./dl), ifosfamide (4,000 mg/m(2)/i.v./dl) and vinorelbine (30 mg/m(2)/i.v./dl) plus G-CSF 300 mu g/s.c. on days 7-12 every 14 days for three cycles before surgery. In 26 evaluable patients, the radiographically assessed response rate to chemotherapy was 77% (8% complete). Three septic deaths (10%) occurred in spite of G-CSF and 1 patient refused to continue after the first cycle. Thoracothomy was performed in 23 patients including 19 complete resections. At 15 months median follow-up (range 10-22+), 11/19 (57%) completely resected patients relapsed. The overall median time to treatment failure was 11 months (range 0-17). Actuarial survival probability at 12, 18 and 24 months are 56%, 43% and 36%, respectively. In conclusion, the combination of cisplatin, ifosfamide and vinorelbine in full doses at a 14 day interval (accelerated chemotherapy) was very effective in neoadjuvant NSCLC setting. Nevertheless, relevant toxicity was demonstrated with a 10% death rate probably due to the overlapping toxicity of chemotherapy cycles, suggesting the need for a more intense supportive care or longer interval between cycles.     

Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. PATIENTS AND METHODS: Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. RESULTS: Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. CONCLUSION: Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity.     

Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): a feasibility study

BACKGROUND: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. PATIENTS AND METHODS: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m2). This was to be followed by 2 cycles of cisplatin/ vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. RESULTS: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. CONCLUSION: Oral vinorelbine 50 mg/m2 (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy.     

非小细胞肺癌患者对术后辅助化疗的评价和选择

[目的]了解已接受术后辅助化疗的非小细胞肺癌（NSCLC）患者对辅助化疗的评价和选择倾向。[方法]调查2006年11月1日-2009年3月31日间接受术后辅助化疗的NSCLC60例。调查内容包括患者对辅助化疗的评价,患者在假设病理ⅠB期、Ⅱ期和Ⅲ A期条件下可接受辅助化疗带来的最小生存率和中位生存期。[结果]93.3％患者认为辅助化疗值得做。约70％患者愿意接受辅助化疗以获得生存期延长1年或者5年生存率提高10％。曾出现化疗重度毒副反应、Ⅲ A期和经济状况差的患者要求辅助化疗带来的生存获益更高。[结论]多数患者能够接受术后辅助化疗带来的益处和毒性反应．     

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy

This prospective, randomized, phase III trial shows that prophylactic cranial irradiation prolongs disease-free survival, decreases the rate of cerebral metastases and does not affect quality-of-life for patients with fully resected postoperative pathologically confirmed stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.BackgroundThis study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA–N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.Patients and methodsIn this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.ResultsThis trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46–0.98;P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14–0.57;P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56–1.16;P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.ConclusionIn patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.     

Long-term evaluation of intrapleural bacillus Calmette-Guerin with or without adjuvant chemotherapy in completely resected stages II and III non-small-cell lung cancer.

Between January 1979 and December 1980, 52 patients with completely resected stages II and III non-small-cell lung cancer (NSCLC) were randomly assigned to receive either adjuvant chemotherapy (cyclophosphamide, doxorubicin, and vincristine--CAV) plus intrapleural bacillus Calmette-Guerin (BCG) (n = 26) or adjuvant CAV alone (n = 26). Careful intraoperative staging was performed in all patients, and stratification for histology (squamous versus nonsquamous) and stage (II or III) ensured a balanced randomization for these factors. With a median follow-up time of 111 months, overall 10-year and median survival were 21% and 20 months (range 2-127 + months), respectively. Thirty-four (95%) patients relapsed in extrathoracic sites, and five (5%) developed loco-regional recurrence; their overall median disease-free interval (DFI) was 10 months (range 1-73 months). There was a 9% and 2.5 month difference in survival (p = .76) and disease-free interval (p = .67), respectively, favoring the BCG arm. There were no significant differences in the sites and patterns of first recurrence comparing the two treatment arms. In conclusion, there is no suggestion of a significant therapeutic advantage from intrapleural BCG in conjunction with adjuvant chemotherapy for completely resected stages II and III NSCLC.     

Long term analysis of survival in the European randomized trial comparing vinorelbine/cisplatin to vindesine/cisplatin and vinorelbine alone in advanced non-small cell lung cancer

In the period 1989-1991, 612 patients with inoperable stage IIIA/B and IV non-small cell lung cancer (NSCLC) were randomized in a phase III trial comparing three chemotherapy regimens. Survival data at five and six years of follow-up confirm the overall benefit of treatment with a combination of vinorelbine and cisplatin compared to vindesine plus cisplatin or vinorelbine alone. Of the 612 patients randomized at the start of the study, 17 have survived beyond five years. Of these patients, eight had entered the trial with metastatic disease. Multivariate analysis to detect prognostic factors suggested a possible interaction between the effect of having cisplatin in the chemotherapy received and baseline performance status. Subgroup analysis subsequently confirmed that the survival benefit of the vinorelbine plus chemotherapy regimen is evident only in patients with initial World Health Organization performance status (PS) of 0-1. Among these patients, the one-year survival rate is 38% for the vinorelbine/cisplatin arm, 29% for vindesine/cisplatin and 34% for vinorelbine alone. The corresponding figures for median survival are 43, 33 and 36 weeks. Among inoperable NSCLC patients with a PS of 2, who appear from this trial not to have benefited from the presence of cisplatin in their chemotherapy, use of single agent vinorelbine is an appropriate treatment option.     

Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer

We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4-84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group.     

非小细胞肺癌术后辅助化疗和靶向治疗的临床疗效对比分析

目的 比较观察术后辅助化疗和易瑞沙用于Ⅲa期非小细胞肺癌(NSCLC)的术后辅助治疗的疗效.方法 入组76例Ⅲa期行完全性切除术的NSCLC,选择口服易瑞沙治疗33例,选择术后辅助化疗43例.治疗结束后分别观察两组的生存情况.结果 易瑞沙组1、2年生存率分别为93.9%和51.5%,化疗组分别为88.4%和48.8%,...     

A phase II study of oral vinorelbine in combination with cisplatin conducted in Taiwan in patients with unresectable localized or metastatic non-small cell lung carcinoma

BACKGROUND: Intravenous vinorelbine plus cisplatin is widely prescribed for the treatment of NSCLC. The objective of this phase II study was to define the efficacy of an oral form of vinorelbine combined with cisplatin for first line treatment of advanced/metastatic NSCLC. PATIENTS AND METHODS: From September 2002 to December 2003, 46 chemotherapy-naive patients received 80 mg/m(2) of cisplatin on day 1 and oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: After an independent panel review, the response rate was 37.5 % [95% confidence interval (CI): 22.7-54.2%] in the evaluable population and 32.6% [95% CI: 19.5-48] in the intent-to-treat population. Median progression-free survival was 5.6 months and overall survival was 11.2 months. Grades 3 and 4 neutropenia was observed in 58.7% of patients, with febrile neutropenia and neutropenic infection in 4.3 and 8.7% of patients, respectively. The main non-haematological toxicities were hypotension, fatigue (8.7% for each) and gastrointestinal disorders with rare grades 3 and 4. CONCLUSIONS: These results suggest that the combination of cisplatin at 80 mg/m(2) on day 1 with oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks, is an active regimen, associated with acceptable toxicity. Oral vinorelbine is therefore a good alternative to the i.v. formulation.