Phase II study of the combination of vinorelbine and cisplatin in advanced non-small-cell lung cancer

Purpose To evaluate the efficacy and safety of combination chemotherapy with cisplatin and vinorelbine for the treatment of previously untreated patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods Eligible patients were those with measurable NSCLC. They were treated with two or more cycles of a regimen consisting of vinorelbine 25 mg/m² on days 1 and 8 and cisplatin 80 mg/m² on day 1 every 3 weeks.Results A total of 45 patients were enrolled. The response rate was 51.1% (23/45; 95% CI 35.8% to 66.3%). The median survival was 286 days with a 1-year survival rate of 40%. The median number of treatment cycles was 2. The major toxic effect was neutropenia of grade 3 or higher (84%). Nonhematological toxicities, including vomiting (62%), were mild (grade 2 or less). There were no treatment-related deaths.Conclusion The high response rate and good tolerability proved this combination therapy to be a safe and effective treatment for advanced NSCLC.This work was supported in part by a grant-in-aid from the Ministry of Health and Welfare (Tokyo, Japan) and from the Second Term Comprehensive 10-Year Strategy for Cancer Control.     

两种不同方案治疗晚期非小细胞肺癌的疗效比较(英文)

Objective: The aim of this study was to analyze and compare the recent efficacy and toxicity of a three-drug platinum-based regimen (A regimen): [cisplatin (DDP) + gemcitabine (GEM) + vinorelbine (NVB)] and a two-drug combination without a platinum drug (B regimen): GEM + NVB, which were used to treat 55 advanced non-small cell lung cancer (NSCLC) patients, in a bid to provide a guidance for clinical treatment. Methods: Twenty-four cases of advanced NSCLC (stage III-IV) patients were treated with A regimen ...     

吉西他滨与紫杉醇分别联合顺铂治疗非小细胞肺癌的对比研究

目的对比吉西他滨与紫杉醇分别联合顺铂化疗初治非小细胞肺癌的疗效和不良反应。方法81例患者随机分为两组,吉西他滨组（GP）：吉西他滨1 000 mg／m² ,d₁,d₈,静脉滴注,顺铂30 mg／m² ,d₂～d₄,静脉滴注,28天为1周期。紫杉醇组（TP）：紫杉醇175mg/ m²,d₁,顺铂30 mg／m² ,d₂～d₄,静脉滴注,28天为1周期。结果GP组总有效率（CR+PR）45.0％（18/40）,TP组43.2％（16/37）,两组近期疗效差异无统计学意义（χ²=0.527,P=0.957）。GP组中位生存期为11月,1年生存率37.7%,而TP组为11月,31.7%,两组生存差异无统计学意义（χ2=0.140,P=0.708）。两组主要不良反应不同,GP组血小板减少症显著高于TP组,而TP组外周神经炎、恶心呕吐和肌痛显著高于GP组。结论吉西他滨与紫杉醇联合分次顺铂治疗非小细胞肺癌疗效相当,但吉西他滨的治疗相关不良反应较轻,可作为初治晚期非小细胞肺癌的一线方案。     

Biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer

Purpose: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new strategies to better use currently available agents. To assess the efficacy and safety of a biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer. Methods: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0–2 and normal organ function were eligible. Treatment consisted of cisplatin 100 mg/m² on day 1 plus gemcitabine, 1,000 mg/m² and vinorelbine 25 mg/m² on days 1 and 15 every 28 days. Results: Of the 40 patients enrolled and assessable for response, there were five (12.5%) with confirmed complete response and 14 (35%) with a confirmed partial response for an overall response rate of 47.5%. Nine patients had stable disease while 12 (30%) progressed. Median progression-free survival and overall survival for all patients were 6.3 and 11.1 months, respectively. Toxicity was principally hematologic, with grade 3–4 neutropenia in 30%, and grade 3–4 nausea/vomiting in 22.5%. There were no treatment-related deaths. Conclusions: The biweekly regimen of cisplatin, gemcitabine and vinorelbine is associated with a high rate of response, lesser toxicity than other three-drug regimens and no benefit of survival. Therefore, the regimen under study may be an appealing alternative when considering other treatment modalities for advanced lung cancer, such as neoadjuvant therapy.     

局部晚期鼻咽癌调强放疗同期化疗前TPF诱导化疗Ⅰ和Ⅱ期临床研究

目的 探讨局部晚期鼻咽癌调强放疗同期化疗前多西泰索加顺铂加氟尿嘧啶方案诱导化疗中顺铂最大耐受剂量(MTD)及方案安全性、有效性。方法 选取 33例局部晚期鼻咽癌患者,通过剂量递增试验确立顺铂MTD并评价临床疗效及不良反应。结果 多西泰索60 mg/m²第1天、氟尿嘧啶550 mg/m²第 1~5天剂量下顺铂MTD为65 mg/m²第1天,每3周重复下3、4级不良反应发生率分别为中性粒细胞降低 67%,粒细胞缺乏性发热9%,腹泻21%,口腔黏膜炎6%。除剂量限制性毒性患者外,其余均完成了治疗。诱导化疗后有效率为97%,其中完全缓解率为21%。结论 鼻咽癌流行地区每3周重复用多西泰索60 mg/m²第1天、顺铂65 mg/m²第1天、氟尿嘧啶550 mg/m²第 1~5天治疗局部晚期鼻咽癌患者是安全有效的。     

Preoperative chemotherapy with cisplatin in combination with docetaxel and gemcitabine in locally advanced non-small-cell lung cancer

Despite surgery, both locoregional and distant disease controls remain poor in stage III non-small-cell lung cancer (NSCLC). Preoperative chemotherapy has become an accepted treatment but no established regimen exists. Our objective was to define the activity and feasibility of cisplatin in combination with docetaxel and gemcitabine in stage III NSCLC followed by surgery or radiotherapy. Thirty-two chemotherapy-naive patients with NSCLC (59% stage IIIAN2, 41% stage IIIB) received cisplatin 75 mg/m² on day 1, gemcitabine 1,000 mg/m² on days 1 and 8, and docetaxel 20 mg/m² on days 1, 8 and 15. Patients received induction chemotherapy (3 cycles) before re-evaluation, followed by thoracotomy or thoracic radiotherapy. Radiographic response was 50% and stable disease at computed tomography (CT) scan was observed in 30% of patients. Thirty patients were evaluable for response; thoracotomy was performed in 16 patients (53%) and resection was complete in 8 patients (27%). Grade 3/4 neutropenia, the main hematologic toxicity, occurred in 53% of patients but only 3 patients required hospitalization due to neutropenic fever. Severe non-hematologic toxicity was uncommon. There were 3 treatment-related deaths. To date, 22% of patients remain alive and disease-free with a median follow-up of 13 months. Median survival for all recruited patients was 14 months, with an estimated 1-year survival rate of 60%. The combination of cisplatin/docetaxel/gemcitabine is a welltolerated regimen. Although it has potential serious toxic effects, high response rates and manageable toxicity justify its use in further trials. The Spanish Lung Cancer Group (SLCG) is currently performing a trial with this regimen in stage III disease.     

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study

Background

The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non–small-cell lung cancer (NSCLC) patients.

Materials and Methods

Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m²) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m²) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results

Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion

Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.     

Phase I/II and Pharmacokinetic Study of Intravenous Vinflunine in Combination With Cisplatin for the Treatment of Chemonaive Patients With Advanced Non–Small-Cell Lung Cancer

BackgroundA multicenter phase I/II trial of vinflunine administered in combination with cisplatin at 80 mg/m² was conducted in order to determine the dose-limiting toxicities, the maximum tolerated dose, and the recommended dose of the combination. An eventual mutual pharmacokinetic drug-drug interaction when vinflunine and cisplatin were coadministered was also evaluated. The study was also intended to define the response rate of vinflunine in combination with cisplatin as first-line chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC) at the recommended dose.Patients and MethodsPatients were required to have a histologically confirmed diagnosis of NSCLC not amenable to curable treatment or stage IV disease. Patients may have had previous surgery for NSCLC but were to be chemonaive and have at least 1 bidimensional measurable lesion outside an irradiated area.ResultsThe recommended dose was established at cisplatin 80 mg/m² combined with vinflunine 320 mg/m². No unexpected adverse events were seen. Pharmacokinetic analysis supported the absence of mutual pharmacokinetic interaction when vinflunine and cisplatin are given in combination. Treatment of 53 patients at this recommended dose demonstrated a tumor response rate of 32.1% in the intent-to-treat population; disease control was achieved in 79.2% of the patients. The median progression-free survival and overall survival were estimated at 5 months and 10.4 months, respectively, and the 1-year survival rate was 43.4%.ConclusionThese results place the vinflunine/cisplatin combination among the most active doublets in this treatment setting and warrant further development in phase III trials of first-line treatment of patients with advanced metastatic NSCLC.     

A phase II study of a novel gemcitabine plus cisplatin regimen administered every three weeks for advanced non-small-cell lung cancer

Background: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC).Patients and methods: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m² and cisplatin was administered at a dose of 100 mg/m² on day 1, every 21 days.Results: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%–82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3–4 in 54% of the patients, and thrombocytopenia grade 3–4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m²/week, and 31 mg/m²/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7–13), 17 patients are still alive and nine have died. The median overall survival is 12 months.Conclusion: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.     

Fever-range whole-body thermal therapy combined with cisplatin,gemcitabine, and daily interferon-α: A description of a phase I-II protocol

Purpose: The purpose of the Phase I component of this study was to find the maximally tolerated dose (MTD) of cisplatin administered within a regimen of fever-range whole body thermal therapy (FR-WB-TT), cisplatin, gemcitabine, and low-dose interferon-alpha (IFN-α). The Phase II component aimed to assess which cancer diagnoses responded to the regimen, the response rate, and response duration.

Materials and methods: The protocol design derived from a schedule-optimized preclinical regimen. Drugs were administered together, and also with thermal therapy in a schedule that optimized the therapeutic index. Eligible patients were those with therapy-resistant, metastatic or advanced solid malignancies. Beginning at 40 mg/m², the cisplatin dose was escalated by 10 mg/m² to the maximally tolerated dose (MTD) in successive cohorts of 3 patients. A treatment cycle consisted of cisplatin on day one, followed by thermal therapy and simultaneous gemcitabine 36 hours later; then a second dose of gemcitabine one week later; and daily IFN- α.

Results: Thirty-seven patients were treated on protocol. The MTD of cisplatin in the thermochemotherapy regimen was established to be 60 mg/m². The dose limiting toxicities (DLT) were peripheral neuropathy and ototoxicity. Complete and partial responses combined were 43%. The therapy improved the quality of life of responding patients.

Conclusion: The protocol was well tolerated and was associated with antitumor activity in patients with a variety of advanced metastatic solid tumors. Tumor response occurred with the thermochemotherapy treatment despite treating malignancies that had progressed on the same chemotherapy drugs administered as standard treatment. Notably, good responses were observed in patients with high-grade neuroendocrine and pancreas cancers. This regimen will be tested in a phase II study.     

Comparative effectiveness study of single high-dose cisplatin with fractionated doses cisplatin in first-line therapy for treatment-naive Chinese patients with advanced non–small-cell lung cancer

BackgroundCisplatin is one of the most effective chemotherapeutic drugs for patients with advanced non–small-cell lung cancer (NSCLC). Single high-dose cisplatin is a commonly used chemotherapy regimen in the world. At present, fractionated doses cisplatin is used in most hospitals in China. Although many doctors have begun to try a single dose of cisplatin, there are still few studies on the comparison of the 2 regimens. This study describes the efficacy and side effects of cisplatin single-dose administration and fractionated doses regimen in the treatment of advanced NSCLC.MethodsA retrospective study was conducted on 219 patients with advanced NSCLC who received chemotherapy with DDP were divided into 2 groups according to the single dose of cisplatin from January 2014 to December 2017. For experimental group, 108 patients were enrolled and received DDP at a dose of 75 mg/m² on day 1. A total of 111 patients were enrolled in the control group, and DDP was administrated at 25 mg/m² on days 1-3. The efficacy, toxicity, and progression-free survival of the 2 groups were observed and analyzed.ResultsIn the experimental group, the numbers of patients who received PR, SD, and PD were 66, 34, and 8 respectively. In the control group, the numbers of patients who received PR, SD, and PD were 18, 77, and 16 respectively. The percentages of patients with a objective response rate response in the experimental group were significantly higher than that in the control group (61.11% vs 16.22%, P < 0.0001). The incidence of III-IV vomiting in the experimental group was lower than that in the control group (11.11% vs 26.13%). The incidence of I-II hiccups in the experimental group was higher than that in the control group (15.74% vs 10.81%). None of the patients had III-IV degree nephrotoxicity. Myelosuppression mainly manifested as leukopenia. In the experimental group, the incidence of I-II degree of leukopenia was 71.30%, and the III-IV degree was 7.41%, which was 74.77% and 11.71 respectively in the control group. A small number of patients have a decrease in mild platelets and hemoglobin.ConclusionFor patients with advanced NSCLC who require chemotherapy with DDP regimen, the short-term effect of single-dose administration of DDP is better than that of fractional small-dose administration. Toxicity can be tolerated and it is worth promoting clinically.     

Randomized Phase III Study of Cisplatin With Pemetrexed and Cisplatin With Vinorelbine for Completely Resected Nonsquamous Non–Small-Cell Lung Cancer: The JIPANG Study Protocol

This trial report describes the background and design for the Japan Intergroup Trial of Pemetrexed Adjuvant Chemotherapy for Completely Resected Nonsquamous Non–Small-Cell Lung Cancer (JIPANG) study (University Hospital Medical Information Network database: UMIN000006737). Various randomized trials have shown the efficacy of postoperative adjuvant chemotherapy regimens that include cisplatin for resected non–small-cell lung cancer (NSCLC), but the optimal regimen is not known. The JIPANG study is a randomized study comparing cisplatin (75 mg/m², day 1) and pemetrexed (500 mg/m², day 1) with cisplatin (80 mg/m², day 1) and vinorelbine (25 mg/m², days 1 and 8) for nonsquamous NSCLC as postoperative adjuvant chemotherapy. A total of 804 patients with pathological stage II to IIIA completely resected nonsquamous NSCLC were enrolled in this study between March 2012 and August 2016. These patients have been randomized in a 1:1 ratio and stratified according to sex (female vs. male), age (< 70 years vs. ≥ 70 years), pathologic stage (II vs. IIIA), mutation of the epidermal growth factor receptor (mutant vs. wild) and institution. Each treatment will be undertaken every 3 weeks until 4 cycles have been completed. The primary endpoint is overall survival and the secondary endpoints are disease-free survival, rate of treatment completion, and incidence of adverse events. This design has 80% power to detect overall survival with a hazard ratio of 0.786 (α = 1-sided 0.05) with 5-year follow-up after registration of the final patient. This study will show a superior regimen for completely resected nonsquamous NSCLC. Biomarker analyses of the JIPANG study are ongoing.     

A multicenter phase I trial of metronomic oral vinorelbine plus cisplatin in patients with NSCLC

The purpose of the present study was to determine the maximum-tolerated doses (MTDs) and the dose-limiting toxicities of a metronomic administration of oral vinorelbine and cisplatin in patients with advanced/metastatic NSCLC. Twenty-six patients with advanced/metastatic NSCLC were enrolled. Escalating doses of vinorelbine (40–70 mg p.o./trice per week) and cisplatin (70–85 mg/m² intravenous infusion) were administered on day 1 every 3 weeks. ΜΤDs were reached at 60 mg thrice/week p.o. for vinorelbine and 85 mg/m² for cisplatin. Grade 4 neutropenia, febrile neutropenia and grade 4 diarrhea were the dose-limiting events during the first cycle of chemotherapy. The most common grade III-IV hematologic toxicity was neutropenia occurring in seven (27%) patients, while non-hematological toxicities were relatively infrequent and mostly of grade I or II. Objective responses were observed in 20.8% of patients with measurable disease. The regimen of metronomic administration and cisplatin is feasible and active in patients with NSCLC.     

Fixed-dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer

Purpose  We investigated the efficacy and toxicity of a 4-week schedule of a fixed dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer (NSCLC). Methods  In this study, 48 patients with previously untreated NSCLC were given combination chemotherapy that consisted of gemcitabine 1,000 mg/m² (10 mg/m²/min fixed dose rate infusion) and cisplatin 25 mg/m², and both drugs were given weekly on days 1, 8 and 15. Results  A partial response and stable disease were observed in 20 patients (41.7%, 95% CI; 27.8–55.6%) and 12 patients (25.0%), respectively. The overall median survival was 10.30 months (range: 7.85–12.74 months). Major toxicities included neutropenia (grade 3 to 4, 29.2%) and infection (grade 3 to 4, 27.1%). Conclusions  Our results indicate that this regimen is a feasible treatment for elderly or poor performance status patients with unresectable NSCLC. Nevertheless, the morbidity due to myelosuppression and infection following this treatment should be carefully considered. G.-W. Lee and M.-H. Kang contributed equally to this work.     

A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial

BackgroundPlatinum-based two-drug combination chemotherapy has been standard of care for patients with advanced nonsmall-cell lung cancer (NSCLC). The primary aim was to compare overall survival (OS) of patients with advanced NSCLC between the two chemotherapy regimens. Secondary end points included progression-free survival (PFS), response, safety, and quality of life (QoL).Patients and methodsPatients with previously untreated stage IIIB or IV NSCLC, an Eastern Cooperative Oncology Group performance status of 0–1 and adequate organ function were randomized to receive either oral S-1 80 mg/m²/day on days 1–21 plus cisplatin 60 mg/m² on day 8 every 4–5 weeks, or docetaxel 60 mg/m² on day 1 plus cisplatin 80 mg/m² on day 1 every 3–4 weeks, both up to six cycles.ResultsA total of 608 patients from 66 sites in Japan were randomized to S-1 plus cisplatin (n = 303) or docetaxel plus cisplatin (n = 305). OS for oral S-1 plus cisplatin was noninferior to docetaxel plus cisplatin [median survival, 16.1 versus 17.1 months, respectively; hazard ratio = 1.013; 96.4% confidence interval (CI) 0.837–1.227]. Significantly higher febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), and grade 1/2 alopecia (59.3% versus 12.3%) were observed in the docetaxel plus cisplatin than in the S-1 plus cisplatin. There were no differences found in PFS or response between the two arms. QoL data investigated by EORTC QLQ-C30 and LC-13 favored the S-1 plus cisplatin.ConclusionOral S-1 plus cisplatin is not inferior to docetaxel plus cisplatin and is better tolerated in Japanese patients with advanced NSCLC.Clinical trial numberUMIN000000608.     

Phase II trial of neoadjuvant chemotherapy with docetaxel,nedaplatin, and S1 for advanced esophageal squamous cell carcinoma

Although standard chemotherapy for esophageal cancer patients is fluorouracil and cisplatin, the prognosis is still unsatisfactory. A new therapeutic regimen combining docetaxel, cisplatin, and 5‐fluorouracil was recently developed to improve both local and distant tumor control. We developed a new regimen of docetaxel, nedaplatin, and S1 (DGS) and previously reported the recommended dose in a phase I dose‐escalation study. We then undertook a phase II study of DGS for advanced esophageal squamous cell carcinoma. Patients with clinical stage IB/II/III disease were eligible. Patients received two courses of chemotherapy: docetaxel 35 mg/m² with nedaplatin 40 mg/m² on day 8, 80 mg/m² S1 on days 1–14, and 2 weeks off. After completion of chemotherapy, patients underwent esophagectomy. The primary endpoint was the completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery [no residual tumor]). We enrolled 32 patients. The completion rate of protocol treatment was 96.9%. During chemotherapy, the most common grade 3 or 4 toxicity was neutropenia (25.0%). No treatment‐related deaths were observed, and the incidence of operative morbidity was tolerable. The overall response rate after chemotherapy was 83.3%. This DGS regimen was well tolerated and highly active. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014626).     

Cisplatin plus Gemcitabine as Adjuvant Chemotherapy for Radically Resected Non–Small-Cell Lung Cancer: A Pilot Study

BackgroundThe combination cisplatin/gemcitabine is one of the most active and well-tolerated regimens in advanced non–small-cell lung cancer (NSCLC). We undertook this pilot study to evaluate postoperative drug delivery and toxicity of cisplatin plus gemcitabine in patients with radically resected stage IB-III NSCLC.Patients and MethodsTwenty-two consecutive patients were treated with cisplatin 80 mg/m² on day 1 and gemcitabine 1200 mg/m² on days 1 and 8 every 3 weeks for 4 planned courses. Most patients (50%) had pathologic stage IIIA disease; all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. The median age was 63 years (range, 56-73 years). Six out of 22 patients (27.3%) had undergone pneumonectomy.ResultsA total of 85 courses of chemotherapy were administered, and the median number of courses was 4 (range, 1-4 courses); twenty-one out of 22 patients received the planned 4 courses of chemotherapy. Chemotherapy caused grade 3 anemia in 1 patient, grade 3 thrombocytopenia in another patient, and grade 3/4 neutropenia in 4 patients; grade 3 vomiting was observed in 3 patients, and grade 3 anorexia and grade 3 asthenia were both observed in 1 patient. No treatment-related deaths occurred. The median delivered dose intensities of cisplatin and gemcitabine were 24.3 mg/m²/week (97.2%) and 700.9 mg/m² weekly (87.5%), respectively.ConclusionThe combination of cisplatin/gemcitabine is a feasible and well-tolerated regimen in the adjuvant setting. Future trials should better define the best strategy in terms of efficacy, toxicity, and quality of life between this combination and the standard regimen, cisplatin plus vinorelbine.     

Salvage treatment of advanced non-small-cell lung cancer previously treated with docetaxel-based front-line chemotherapy with irinotecan (CPT-11) in combination with cisplatin

Background:A phase II study was conducted in order to determinethe toxicity and efficacy of the combination of CPT-11 and cisplatin, assalvage treatment in patients with advanced non-small-cell lung cancer(NSCLC), progressing after a docetaxel-based front-line regimen. Patients and methods:Thirty-one patients (median age 61 years)with NSCLC, were enrolled. Twenty-six (84%) patients were male,twenty-five (81%) had disease stage IV, and twenty-eight (90%)had a performance status (WHO) 0–1. CPT-11 was administered as a60-minute i.v. infusion at the dose of 100 mg/m² on day 1 and 110mg/m² on day 8; cisplatin was administered at the dose of 80mg/m² on day 8, after CPT-11 administration. Treatment was repeatedevery three weeks. Results:A total of 110 chemotherapy cycles were administered. Inan intention-to-treat analysis 7 patients (23%; 95% confidenceinterval (95% CI): 8%–37%) achieved a partialresponse, 6 (19%) had stable disease, and 18 (58%) progressivedisease. Three of responders had failed a previous docetaxel–carboplatincombination. The median duration of response was 3 months, the median TTP 8months and the median survival for the entire group 8 months. Grade 3–4neutropenia was observed in 16 (52%) patients and in two cases this wasfebrile. Grade 3 and 4 thrombocytopenia occurred in two (7%) patients,respectively. Grade 3 and 4 diarrhea was seen in 10 (33%) patients,grade 2–3 neurotoxicity in 2 (6%), and fatigue grade 2–3in 12 (39%). Other toxicities were mild. Conclusions:The combination of CPT-11 and cisplatin hasmanageable toxicity and interesting activity as salvage treatment of patientswith advanced NSCLC, previously treated with a docetaxel-based front-lineregimen.     

Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

Purpose

To determine the maximum-tolerated dose (MTD) of a 24-h continuous infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer.

Methods

Patients with advanced gastric adenocarcinoma (n = 21) received a weekly regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of docetaxel and cisplatin were fixed at 33.3 and 30 mg/m², respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m² to the MTD.

Results

A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m². All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3–4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 partial responses for an overall response rate of 26% (95% CI: 6–46%). This rate increased to 39% (95% CI: 12–66%) in 13 chemotherapy-naïve patients.

Conclusions

A consecutive weekly DCF regimen at 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity profile. The recommended doses are 33.3 mg/m² of docetaxel, 30 mg/m² of cisplatin and 1,500 mg/m² of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial.     

Cisplatin plus continuous infusion vinorelbine for the treatment of advanced non-small cell lung cancer: a phase I-II study

Backbround In this Phase I/II trial, the maximum-tolerated dose (MTD) and activity of cisplatin plus vinorelbine (VRL) administered in continuous in-fusion as first-line treatment of advanced non small cell lung cancer (NSCLC) was determined in 12 consecutive chemotherapy-naive patients with advanced NSCLC. Patients and methods The dose of cisplatin was 100 mg/m² in all patients, and vinorelbine was administered as an initial intravenous (iv) bolus of 8 mg/m² on day 1 followed by a 4-day continuous iv infusion at 4 different 24 h dose levels (DLs) to be repeated every 21 days. All 12 patients (47 cycles) were evaluable for response and toxicity. Results The MTD was 8 mg/m² bolus followed by a continuous iv infusion of 8 mg/m² per day over 4 days. The dose limiting toxicities (DLT) were febrile neutropenia in 4 patients and grade 3 mucositis in 1 patient. There was less neuro-toxicity and compared to the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Partial responses were observed in 6 patients; an overall response rate of 50% (95% CI: 30–65%). Median time to progression was 5,5 months (95% CI: 1,5–11 months) and median survival was 11 months (95% CI: 5–20 months). Conclusions The results demonstrate that, in this setting of first-line treatment of NSCLC, cisplatin plus vinorelbine at 8 mg/m² bolus followed by a continuous infusion of 8 mg/m² per day over 4 days is the recommended schedule. Further trials would be useful to establish activity of this combination.