A Cisplatin and Vinorelbine (NP) Regimen as a Postoperative Adjuvant Chemotherapy for Completely Resected Breast Cancers in China: Final Results of a Phase II Clinical Trial

Objective: To evaluate the efficacy and toxicity of cisplatin and vinorelbine (NP) for postoperative adjuvantchemotherapy of completely resected breast cancers. Methods: Between September 1994 and April 2005, 91Chinese breast cancer patients, with pathologically-confirmed adenocarcinoma in Jiangsu Cancer Hospitaland Research Institute, were enrolled. They received postoperative vinorelbine at 25mg/m2 on days 1 and 8,and cisplatin 25mg/m2 on days 1 to 3, this regimen being repeated every 3 weeks. Results: Median age was 49years (range, 25-69 years). A ccording to the TNM stage system, stage Ⅰ, Ⅱ, ⅢA patients accounted for 7.7%,58.2% and 34.1%, respectively. The median number of chemotherapy cycles was 4.5 (range, 1-8), over half ofthe patients receiving 4 to 6 NP cycles. After a median follow-up of 48 months, 11 deaths and 29 relapses weredocumented. Median disease-free survival was 45 months, with disease-free and overall survival at 5 years being76% and 88.7%, respectively. All patients could be evaluated with regard to toxicity, 17 (18.7%) developing gradeⅢ neutropenia during treatment, but all recovering after recombinant human granulocyte colony stimulatingfactor (G-CSF) injection, 3 suffering thrombocytopenia (3.3%), 5 anemia (5.5%) and 5 nausea/vomiting (5.5%).No treatment related deaths occurred. Conclusions: NP is an effective and feasible treatment for completelyresected breast cancer cases at the doses tested. A randomized clinical trial is now needed to compare NP withother conventional regimens.     

Post-operative Treatment with Cisplatin and Vinorelbine in Chinese Patients with Non-small Cell Lung Cancer: A Clinical Prospective Analysis of 451 Patients

Purpose: To determine the efficacy of post-operative chemotherapy with cisplatin plus vinorelbine (NP) inChinese patients with non-small cell lung cancer (NSCLC). Methods: A total of 451 patients with NSCLCs atstages I, II, and IIIA after surgical resection were treated with cisplatin plus vinorelbine for 4 cycles or volunteersobserved between January 2002 and November 2004 and were followed for five years. The therapeutic efficacywas evaluated with reference to overall survival (OS) and disease-free survival (DFS), and adverse effects werealso recorded. Potential factors affecting the lengths of OS and DFS were analyzed by multivariate analysis.Results: Most patients (86.7%) completed at least 4 cycles of treatment. Patients with chemotherapy survivedsignificantly longer than those in the observation group (p<0.001). The absolute improvements in the 2 and 5-yearOS were 3.8% [hazard ratio (HR) =0.674, 95% confidence interval (CI): 0.554-0.820, P<0.0001] and 13.0%(HR=0.732, 95% CI: 0.579-0.926, P=0.009), respectively. The improvement at 4-year DFS was 2.1% (HR=0.327,95% CI: 0.214-0.500, P<0.0001). Stratification analysis revealed that older age, histological type, pathologicaldegree, but not the gender and smoking status, are independent factors affecting the length of survival in thispopulation. Many patients (63.3%) had grade 1-III tolerable adverse effects, and there was no treatment-relateddeath. Conclusions: Post-operative chemotherapy with NP regimen is effective and tolerable in Chinese patientswith NSCLC.     

EARLY [18F]FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY–BASED RESPONSE EVALUATION AFTER TREATMENT WITH GEMCITABINE AND VINORELBINE FOR REFRACTORY HODGKIN DISEASE: A CHILDREN’S ONCOLOGY GROUP REPORT

The International Harmonization Project defined complete response (CR) after treatment for Hodgkin disease (HD) by absence of fluorodeoxyglucose avidity, regardless of the size of residual masses. Residual avidity after initial treatment is known to predict inferior survival. In the setting of retrieval therapy, early positron emission tomography (PET) scans may improve assessment of treatment efficacy. Retrospective analysis after 2 cycles of gemcitabine and vinorelbine for refractory HD revealed 6 CR among 13 patients by PET and 1 CR in 13 by computed tomography (CT). No relationship between PET response and event-free or overall survival could be discerned, presumably because of the heterogeneity of subsequent therapies.     

Weekly Vinorelbine and Docetaxel as Second-Line Chemotherapy for Pretreated Non-Small Cell Lung Cancer Patients: a Phase I-II Trial

Abstract

Docetaxel was proven to be effective as second-line therapy for patients with advanced NSCLC after failure of platinum-based front-line chemotherapy. We designed this phase I/II study to define the Maximum Tolerated Dose of weekly docetaxel combined with weekly vinorelbine, and subsequently evaluate tolerability and activity of this schedule in NSCLC patients who were progressive after treatment with either cisplatin and gemcitabine or carboplatin and paclitaxel regimens. To be eligible for the study, patients were required to have a WHO performance status ≤2, failure after at least two cycles of first platinum-based chemotherapy, and no prior treatment with docetaxel and vinorelbine. A total of 27 patients were enrolled in this phase I/II study. A weekly docetaxel dose of 25 mg/m² was recommended in combination with fixed vinorelbine dose of 20 mg/m², and 24 patients were treated at this dose level. Severe neutropenia (62%) and febrile neutropenia (29%) were the most frequent toxicities, with 83% of patients requiring dose modification or delay. In the phase II study, 5 (21%) patients obtained a partial response, 8 (33%) patients had stable disease, whereas 10 (42%) patients progressed. After a median follow-up of 18.7 months, median survival was 8 months, with 30% surviving at 1 year. Regardless of the use of weekly docetaxel schedule, this regimen was highly myelosuppressive, and did not seem to improve response rate and survival compared to single-agent docetaxel. No further developments of this schedule are warranted.     

长春瑞滨节拍化疗在晚期非小细胞肺癌患者中的应用

传统化疗依靠常规剂量静脉给药,毒性较大,肿瘤易复发和耐药,而节拍化疗低剂量、频繁、短间歇给予细胞毒性药物的治疗方式在一定程度上减少了化疗不良反应,延缓了肿瘤的复发、耐药;节拍化疗通过抗血管生成、免疫调节、抑制肿瘤干细胞并诱导肿瘤细胞休眠抑制肿瘤生长。口服长春瑞滨节拍化疗在晚期非小细胞肺癌患者治疗中有多种应用方案,包括单药化疗、双药化疗、联合抗血管生成药、联合靶向治疗、联合放疗、联合免疫治疗等多种治疗方案。     

盖诺化疗患者不同静脉注射通路局部毒性反应比较

目的比较盖诺化疗患者不同静脉注射通路局部毒性反应,为患者寻找安全有效的化疗静脉通路。方法将59例使用盖诺化疗的患者,按血管的情况分为前臂静脉组28例和颈外静脉组31例,分别使用前臂静脉和颈外静脉穿刺静脉留置针注射盖诺。比较两组给药过程中局部疼痛和化疗性静脉炎的发生情况。结果颈外静脉组局部疼痛、化疗性静脉炎发生率明显低于前臂静脉组（P〈0.01）。结论接受盖诺化疗的患者通过颈外静脉留置针给药,较前臂静脉留置针给药安全可靠,能有效控制局部疼痛、化疗性静脉炎的发生。     

洛铂联合长春瑞滨治疗晚期非小细胞肺癌的临床观察

背景与目的：化疗是晚期非小细胞肺癌（NSCLC）的主要治疗手段,但顺铂（DDP）和卡铂（CBP）的毒性较大,患者对化疗的耐受性及依从性较差。洛铂（LBP）是第3代新型铂类抗癌药,国外研究表明LBP与DDP的抗癌活性相似,但肾毒性和胃肠道反应较轻,且可能对部分DDP耐药的肿瘤患者有效。本研究观察国产LBP联合长春瑞滨（诺维本,NVB）治疗晚期NSCLC的疗效和不良反应。方法：64例经病理组织学证实的NSCLC初治患者,临床分期Ⅲ8～Ⅳ期,随机分为NL组（NVB＋LBP）和即组（NVB＋DDP）;NL组LBP 30mg／m^2静滴,第1天,NVB 25mg／m^2,陕速静滴,第1,8天;NP组顺铂（DDP）30mg／m^2静滴,第2～4天,NVB25mg／m^2快速静滴,第1,8N,2组均21～28d为1个周期,连用3个周期后进行疗效评价,观察中位生存时间。结果：NL组34例中,CR1例,PR 13例,NC15例,PD5例,有效率（RR）41．2％,疾病控制率（DCR）85．3％;NP组RR43．3％,DCR 83．3％（X^2=0．05,P〉0．05）;中位生存时间NL组8．6个月,XP组8．9个月（P〉0．05）。NL组主要毒性反应为骨髓抑制,消化道反应如食欲不振（X^2=4．69,P〈0．05）及恶性、呕吐较XP组为轻（X^2=7．43,P〈0．01）,未发现明显的肝肾毒性、周围神经毒性等。结论：国产LBP联合NVB治疗晚期NSCLC的疗效与DDP联合NVB相当,但不良反应较轻,耐受性好。     

Phase II study of an all-oral combination of vinorelbine with capecitabine in patients with metastatic breast cancer

Purpose  Combination of intravenous (i.v.) vinorelbine and capecitabine was shown to be feasible and effective in metastatic breast cancer (MBC). In an effort to improve patient convenience and to prolong infusion-free survival, we investigated in first-line treatment a regimen combining oral vinorelbine and capecitabine in a phase II study. Patients and methods  Fifty-two patients (median age, 60 years) with MBC received the combination consisting of oral vinorelbine 60 mg/m² on days 1, 8 and 15 plus capecitabine 1,000 mg/m² bid given from day 1 to day 14 in an open-label, multicentre phase II study [the recommended doses were established in a phase I study (Nolé et al. in Ann Oncol 17:332–339, 2006)]. Cycles were repeated every 3 weeks. Results  Seventy-nine percent of the patients had received prior adjuvant chemotherapy and 81% presented with visceral involvement. The median number of administered cycles per patient was 7 (range 1–18). Twenty-three responses were documented and validated by an independent panel review, yielding response rates of 44.2% (95% CI, 30.5–58.7) in the 52 enrolled patients and 54.8% (95% CI, 38.7–70.2) in the 42 evaluable patients. Median progression-free survival and median overall survival were 8.4 and 25.8 months, respectively. Neutropenia was the main dose-limiting toxicity but complications were uncommon, only one patient having experienced febrile neutropenia. Other frequently reported adverse events included, fatigue, nausea, vomiting, diarrhoea and constipation, stomatitis and hand-foot syndrome, which were rarely severe. Conclusions  This regimen combining oral vinorelbine with capecitabine is effective and manageable in the first-line treatment of MBC. Oral vinorelbine on days 1, 8 and 15 with capecitabine from days 1 to 14 every 3 weeks represents a convenient option which offers an all-oral treatment to the patients and prolongs their infusion-free survival.     

Bleomycin, vinorelbine and trofosfamide in relapsed stage IV cutaneous malignant melanoma patients

Purpose  To evaluate the efficacy of bleomycin, vinorelbine, and trofosfamide (BVT) in 28 patients with pretreated relapsed AJCC stage IV cutaneous malignant melanoma. Methods  Patients in relapse after first- or second-line therapy received 8 mg/m² intravenous (i.v.) bleomycin, 25 mg/m² i.v. vinorelbine, on days 1 and 6, each, and oral (p.o.) trofosfamide 60 mg/m²/day, days 1–7. BVT therapy was repeated every 5 weeks until progression of disease occurred. A maximum of six BVT cycles (mean, 2.2 cycles) was administered per patient. Results  Three patients (11%) reached a partial response; 5 (18%) patients showed stable disease, and 20 (71%) patients progressed upon BVT therapy. Median overall survival of all 28 patients was 6 months (6-month survival rate, 52%). Patients with partial remission or stable disease (n = 8) exhibited a median overall survival of 10 months (6-month survival rate, 75%), while patients with disease progression (n = 20) showed a median overall survival of 3 months (6-month survival rate, 43%). Most side effects were limited to WHO grade I/II mild anemia, leucocytopenia, fatigue, nausea/vomiting, pain, and anorexia. WHO grade III/IV side effects occurred in 7% (anorexia) and 4% (fatigue) of patients. Conclusion  Treatment with BVT was efficient in 29% of pretreated relapsed stage IV cutaneous melanoma patients, with overall good tolerability and safety.     

Efficacy, toxicity and cost analysis for non-platinum triplet (gemcitabine and vinorelbine, followed by docetaxel) vs. platinum-based chemotherapy in IIIB/IV non-small-cell lung cancer: single-institution experience

A new non-platinum sequential triplet combination chemotherapy regimen, comprising gemcitabine (1000 mg/m²) and vinorelbine (25 mg/m²), followed by docetaxel (60 mg/m²), was compared in terms of efficacy, toxicity and cost with platinum-based chemotherapy regimens (comprising cisplatin plus one or more other anti-tumour drugs) for the treatment of advanced non-small-cell lung cancer in a matched, small-sample size, case–control study. Patients were selected from a single institution. Patients in the platinum and non-platinum groups were matched for clinical stage (IIIB/IV), performance status (0/1), age and sex. For the non-platinum and platinum groups, the overall response rates were 40% and 47%, and the median survival times were 14 and 14.5 months respectively. The most common grade 3–4 toxicity was neutropenia (27%) in the non-platinum group and nausea/vomiting (67%) in the platinum group. The total treatment cost did not differ significantly between the two groups. The non-platinum sequential triplet combination chemotherapy regimen studied was shown to be as effective as the traditional cisplatin-based combination chemotherapy regimen, and was associated with less toxicity.