An early phase II trial combining cisplatin, carboplatin and vindesine in patients with inoperable non-small cell lung cancer

We conducted an early phase II trial of advanced non-small cell lung cancer (NSCLC) to evaluate the response efficacy of a combination of cisplatin (CDDP), carboplatin (CBDCA) and vindesine (VDS). The twenty-four patients in the study had had no previous treatment. CDDP (15 mg/m2), CBDCA (200 mg/m2) and VDS (3 mg/m2) were administered on Day 1, CDDP (15 mg/m2) was administered on Days 2-5, and VDS (3 mg/m2) was administered on Day 8. We observed 9 partial responses (PR), with a total response rate of 39%. The overall median survival was 72 weeks, and the 1-year survival rate was 57%. Major toxicities were hematologic; leukopenia of grades 3 and 4 occurred in 25% patients, and thrombocytopenia occurred in 21%. Therefore, the combination of CBDCA with CDDP and VDS chemotherapy was effective against inoperable NSCLC with tolerable toxicities and a favorable median survival time.     

Cisplatin, ifosfamide and vindesine in the chemotherapy of squamous cell carcinoma of the lung

Thirty-one patients with inoperable squamous cell carcinoma of the lung were treated with a combination of cis-platin (CDDP, 100 mg/m2 day 1), ifosfamide (IFX, 2 g/m2 day 1, 2, 3; with mesna) and vindesine (VDS, 3 mg/m2 day 1). The overall response rate (PR) was 71.0% with 22 partial responses. The median duration of response was 180 days. The median duration to show 50% decrease was 29 days. Myelosuppression and renal toxicity were severe. We concluded that the CIV regimen against squamous cell carcinoma of the lung was more effective yet more toxic than the other regimen containing CDDP and that candidates for this therapy must be carefully chosen.     

Cis-dichlorodiammine platinum (II) CDDP in the treatment of non-small cell lung cancer

The effect of CDDP was evaluated in 44 cases of non-small cell lung cancer (squamous cell ca. 11 cases, adeno-large cell ca. 33 cases). Administered dosage of CDDP was in the range of 60-100 mg/m2 (60 mg/m2, 80 mg/m2, 100 mg/m2 per individual). 23 cases were treated with CDDP chemotherapy alone while the other 21 cases were combined with Vindesine (VDS). Three cases out of 18 receiving the CDDP monochemotherapy achieved partial response and the response rate was 16.7%. Six cases out of 15 receiving the CDDP + VDS cases achieved partial response and the response rate was 40.0%. Because of slow shrinkage of the lesion as revealed by chest X-ray film, evaluation of CDDP efficacy could only be done after two administrations at 3-4 week intervals. Values of serum creatine and BUN were transiently elevated with a dose-dependent tendency in the monochemotherapy cases. In combination chemotherapy cases bone marrow toxicity was the main dose-limiting factor. This regimen was tolerable and it was concluded that CDDP is a useful agent for combination chemotherapy of non-small cell lung cancer.     

A randomized study of cisplatin versus cisplatin plus vindesine for non-small cell lung carcinoma.

Between August 1983 and March 1985, a randomized study was conducted that compared cisplatin (CDDP) (80 mg/m2 on day 1) alone with CDDP plus vindesine (VDS) (3 mg/m2 on days 1, 8, and 15) in 160 consecutive patients with inoperable non-small cell lung cancer (NSCLC). There were no complete responses. The response rate for CDDP plus VDS (22 of 77 patients, 29%) was significantly higher than that for CDDP alone (9 of 78 patients, 12%) (P less than 0.05). However, no difference existed in the median duration of response (20 weeks for CDDP plus VDS versus 20 weeks for CDDP alone) or the median survival time (45 weeks for CDDP plus VDS versus 39 weeks for CDDP alone). No significant differences in toxicity were detected between the two arms; myelosuppression, alopecia, and peripheral neuropathy occurred more frequently with CDDP plus VDS and there was one lethal episode of hepatorenal syndrome in the CDDP plus VDS arm. Among the variables Eastern Cooperative Oncology Group (ECOG) performance status (PS), age, sex, stage, weight loss, serum lactate dehydrogenase (LDH) level, albumin level, histologic cell type, and chemotherapy arm, only chemotherapy arm was a significant factor leading to a major response (P = 0.019, multiple logistic regression analysis). The significant predictors of survival were PS (P = 0.000), sex (P = 0.000), and stage (P = 0.002) (Cox's proportional hazards model), with a PS of 0 or 1, female sex, and lower stage yielding the best survival. Although a significantly higher response rate was obtained in the combination arm than in the single agent arm, the survival benefit to patients receiving such combination chemotherapy was not determined and more effective chemotherapy regimens are required.     

A phase I/II trial of cisplatin, docetaxel and ifosfamide in advanced or recurrent non-small cell lung cancer

This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.     

Vinorelbine and alternating cisplatin and ifosfamide in the treatment of non-small cell lung cancer

In order to explore the activity of a combination of vinorelbine (VNL) and alternating cisplatin (CDDP) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), a phase II study was performed. Seventy chemoradiotherapy naive patients with NSCLC, stage IIIA, IIIB and IV disease, PS (ECOG) 相似文献   

Adriamycin, cyclophosphamide, vincristine and methotrexate combination chemotherapy of small cell lung cancer

Twenty-two patients who had not received previous chemotherapy for small cell lung cancer were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cyclophosphamide (500 mg/m2, i.v., on day 1, and 350 mg/m2, i.v., on day 8), vincristine (1 mg/m2, i.v., on day 1) and methotrexate (20 mg/m2, i.v., on days 1 and 8). This chemotherapy regimen was repeated at 3- or 4-week intervals. Among 20 evaluable patients, none showed complete response but 14 (70%) showed a partial response, with a median response duration of 8 weeks (range, 4-20 weeks). The median survival time for the 20 evaluable patients was 28 weeks. Toxicity included mild to moderate hematologic toxicity, alopecia and nausea and vomiting. This combination chemotherapy appears to be suboptimal for the treatment of small cell lung cancer, with no complete responses and a relatively short median survival time.     

Phase II studies of a single agent and a cis-platinum-based two-drug combination in patients with non-small cell lung cancer

Phase II studies of single agent and CDDP-based two drug combination were performed in 189 patients with inoperable non-small cell lung cancer. Six drug regimens were performed: CDDP alone, VDS alone, Epi-ADM alone, CDDP + VDS, CDDP + CPA, CDDP + ADM. The response rates were 15.4% (6/39) with CDDP alone, 8.0% (2/25) with VDS alone, 6.1% (2/33) with Epi-ADM alone, 26.7% (8/30) with CDDP + VDS, 14.3% (4/28) with CDDP + CPA, 17.6% (6/34) with CDDP + ADM and one CR was performed with CDDP + ADM. In patients with no prior chemotherapy, the response rates were 20.0% (6/30), 11.8% (2/17), 12.5% (2/16), 26.7% (8/30), 16.0% (4/25) and 25.0% (3/12), respectively. The median survival times were 25, 27, 23, 33, 25, and 45 weeks, respectively. The efficacy of CDDP in non-small cell lung cancer patients was re-confirmed, and that of CDDP + VDS, CDDP + ADM was suggested. No death due to toxicity occurred and toxicity was generally tolerable.     

Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer

Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.     

VP16, epirubicin and procarbazine in the treatment of advanced non-small-cell lung cancer

We report the results obtained in the treatment of 52 advanced non-small-cell lung cancer patients with the combination chemotherapy VP16 (120 mg/m2 i.v., days 1-2-3), epirubicin (50 mg/m2 i.v., day 1) and procarbazine (100 mg/m2 p.o., days 1 through 8). The courses were repeated every 21 days. No patient had been pretreated. A median of 5 courses was administered. Partial response was obtained in 33% and no change in 21% of patients. Median remission time was 6.5 months, and median survival of responders was 10 months. The best response rate and median survival were obtained in the lowest grade performance status patients and in locally advanced disease patients. Major chemotherapy related toxicities were grade 1-2 leukopenia and grade 2-3 alopecia.     

Vinorelbine, ifosfamide, and cisplatin combination as salvage chemotherapy in advanced non-small cell lung cancer

BACKGROUND: Platinum-based chemotherapy improves survival and quality of life as compared with the best supportive care alone in advanced non-small cell lung cancer. In addition, several recent studies using new drugs such as docetaxel have demonstrated that second-line chemotherapy may be of value. METHODS: We studied the efficacy of combination treatment with vinorelbine, ifosfamide, and cisplatin (NIP) as salvage chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). From March 1998 to December 1999, 44 previously treated patients (etoposide/cisplatin (EP): 36, EP--> taxane/cisplatin: 8) were treated with a chemotherapy regimen consisting of vinorelbine (25 mg/m(2) i.v. on days 1, 15 and 12.5 mg/m(2) i.v. on day 8), ifosfamide (3 g/m(2) i.v. on day 1 with mesna) and cisplatin (60 mg/m(2) i.v. on day 1). The cycles were repeated every 4 weeks. RESULTS: All patients were evaluable for response. The median follow-up duration was 19.1 months (range, 4.4-28.3 months). The objective response rate was 27.3% (95% CI, 14.1%-40.5%) with one complete response and 11 partial responses. The median response duration was 4.1 months (range, 1.5-13 months). The median time to progression was 2.9 months (range, 0.7-15.3 months). The main toxicity was hematologic in the 138 evaluable courses, granulocytopenia (>or=grade III) and anemia (>or=grade III) were observed in 3.6% and 0.7% of the patients, respectively. Non-hematologic toxicities were minor and easily controlled. Four episodes of febrile neutropenia were reported. There were no treatment-related deaths. CONCLUSION: In this study, the combination of vinorelbine, ifosfamide and cisplatin showed a significant efficacy with acceptable toxicities as salvage chemotherapy in previously treated advanced NSCLC patients.     

A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors

In order to evaluate the activity and toxicity of a three-drug combination of vindesine, ifosfamide and cisplatin (VIP) for inoperable non-small-cell lung cancer (NSCLC), we conducted a randomized trial comparing VIP with a two-drug combination of cisplatin and vindesine (VP). Between September 1987 and March 1992, a total of 132 patients with stage III or IV NSCLC were randomly allocated to either VIP or VP. The VIP regimen consisted of vindesine (VDS 3 mg/m(2) on days 1 and 8), ifosfamide (IFX 1300 mg/m(2) on days 1-5), and cisplatin (CDDP 20 mg/m(2) on days 1-5). The VP regimen consisted of VDS and CDDP with the same dose and schedule as the VIP regimen. Both regimens were repeated every 4 weeks. Objective response rates were 49.3% (95% confidence interval: 95%CI, 43.1-55.4%) in the VIP arm and 44.6% (95%CI, 38.4-50.2%) in the VP arm; the difference was not significant (P=0.5390). Median response duration, median survival time, and two-year survival rates were 26.5 weeks, 49.6 weeks, and 14.9% in the VIP arm and 28.7 weeks, 37.1 weeks, and 12.3% in the VP arm, respectively. There were also no significant differences between these two treatment arms. In comparison with the VP regimen, however, a survival advantage of the VIP regimen could be confirmed when the data were evaluated with Cox's multivariate analysis (P=0.0131). In both arms, the principal toxicity was myelosuppression, which was significantly more frequent in the VIP arm, although generally well tolerated. CONCLUSION: This study suggested the survival advantage of the VIP regimen over the VP regimen for treatment of patients with advanced NSCLC.     

Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer]

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.     

Adriamycin, cisplatin, and etoposide combination chemotherapy for small cell lung cancer

Twenty-three patients with small cell lung cancer (11 with limited disease and 12 with extensive disease) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated at 3- or 4-week intervals for 3 to 5 treatment cycles. Among 22 evaluable patients, 5 showed complete response and 17 had a partial response (response rate 100%). The median response duration of 12 extensive disease patients was 21 months. There were 5 survivors for more than 2 years. Toxicity included moderate to severe hematologic toxicity, alopecia, nausea and vomiting. This combination chemotherapy appears to be optimal for the treatment of small cell lung cancer.     

吉西他滨联合顺铂治疗复发性晚期头颈部癌的临床研究

 目的 评价吉西他滨联合顺铂治疗复发性晚期头颈部肿瘤的疗效及毒副作用。方法 对复治的晚期头颈部肿瘤患者，给予GEM 1000mg／m²静滴，第1、8d，每周期CDDP 60mg／m²，静滴（分5次第1-5d），21d为1周期，2周期后评定疗效，平均3．52个周期。结果 27例可评价疗效，完全缓解1例，部分缓解7例，总有效率29．63％，中位缓解期4．4个月，中位生存期9个月。毒副作用主要为剂量限制性毒性，表现为骨髓抑制。结论 吉西他滨加顺铂可作为复发性晚期头颈部肿瘤的挽救性化疗方案。     

Radiotherapy combined with cis-diammine-dichloro platinum (II) plus vindesine in the treatment of non-small cell lung cancer: a comparison with treatment by radiation alone

The effect of CDDP + VDS has been evaluated in 39 cases of non-small cell lung cancer, compared with those treated with radiation alone. Nineteen cases consisted of a combined radiation and chemotherapy group, while twenty cases were classed a the radiation therapy only group. CDDP was given at a dosage of 60 to 110 mg/m2 every 4 weeks, and VDS at a dosage of 3 mg/m2 3 times weekly. Radiation was given at a fraction dose of 1.5 to 2 Gy 5 times per week with a mean total dose of 56 Gy in the radiation only group, and 50 Gy in the combined therapy group. There were no significant difference in both the response rate and the survival time between the two groups. This suggests that combined chemotherapy was not effective for the treatment of non-small cell lung cancer.     

Cisplatin,ifosfamide and vindesine in the chemotherapy of non-small-cell lung cancer: a combination phase II study

Summary A total of 47 patients with unresectable non-small-cell lung cancer were treated with a regimen consisting of cisplatin (CDDP, 100 mg/m²), ifosfamide (IFX, 2 g/m² × 3; with mesna) and vindesine (VDS, 3 mg/m²) (CIV). This regimen was given over a 3- or 5-week period. Among 40 completely evaluable patients, 19 partial responses (PRs) were observed, for a response rate of 47.5% (78.6% in squamous-cell carcinoma and 30.1% in adeno-and large-cell carcinoma); no complete responses (CRs) were obtained. The hematologic toxicity was not severe, but the renal toxicity was rather high; two patients developed acute renal failure and died of subsequent pancytopenia and sepsis. We concluded that the CIV regimen was more effective, especially against squamous-cell carcinoma, but more toxic than the combination of CDDP and VDS for non-small-cell lung cancer and that candidates for this therapy must be carefully chosen.     

Cisplatin, doxorubicin and vindesine in the treatment of advanced non-small cell lung cancer]

Thirty-seven patients with advanced non-small cell lung cancer were enrolled to evaluate a combination chemotherapy of cisplatin (80 mg/m2), doxorubicin (30 mg/m2) and vindesine (2 mg/m2 x 3). The overall response rate was 27% with ten partial remission. The median survival of whole patients was 11.4 months. The calculation of median survival of the patients with partial remission has not been completed: nine of ten patients have been still alive during the follow-up period of 4 to 16 months. The survival of the patients with PR was significantly different from those of the patients with NC or PD. The major toxicity was myelosuppression. These results indicate that a combination chemotherapy with cisplatin, doxorubicin and vindesine is a moderately effective regimen against non-small cell lung cancer compared to others.     

异长春花碱加异环磷酰胺加顺铂联合化疗治疗晚期非小细胞肺癌

目的 评价异长春花碱加异环磷酰胺加顺铂（NIP）联合方案作为第一线化疗对晚期非小细胞肺癌病人的疗效及毒副作用。方法 化疗方案包括异长春花碱25mg/m^2 20min静脉输注第1d和第8d,异环磷酰胺1．2g/m^2 3h静脉输注第1－3d,美司纳400mg-800mg于0、4、8h静脉推注第2－3d,顺铂25mg/m^2 2h静脉输注第1－3d。每3周重复疗程。结果 共54例病人进行本项研究。51例可评价疗效,54例可评价毒性反应。总缓解率为53％,3例（6％）完全缓解,24例（47％）部分缓解。16例（31％）肿瘤稳定,8例（16％）肿瘤发展。中位缓解期7个月,全组中位生存期10个月。本化疗方案的剂量限制毒性为骨髓抑制,其中72％的病人发生3－4度中性粒细胞下降。结论 NIP是治疗晚期非小细胞肺癌有效的联合化疗方案,毒性反应能够耐受,值得进一步研究。     

Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: a Hellenic Cooperative Oncology Group (HeCOG) Phase II study

PURPOSE: To evaluate the efficacy of temozolomide (TMZ) combined with cisplatin (CDDP) in terms of response rate, time to progression (TTP) and overall survival (OS), as well as the tolerability of the regimen in patients with brain metastases from solid tumors. PATIENTS AND METHODS: Patients (n=32) with brain metastases were treated with TMZ 150 mg/m2/day (chemotherapy-pretreated) or 200 mg/m2/day (chemotherapy-naive) for 5 days, combined with CDDP 75 mg/m2 on day 1, every 28 days. Primary tumor sites included breast cancer (n=15), lung cancer (n=12) and other (n=5). Twenty-seven patients had received prior chemotherapy for extracranial disease and 17 had prior radiotherapy to the brain. RESULTS: One patient (3.1%) with non-small cell lung cancer (NSCLC) achieved complete response. Nine patients (28.1%; six with breast cancer, two with melanoma and one with NSCLC) achieved a partial response and five patients (16%) had stable disease. Median OS was 5.5 months and median TTP 2.9 months. One patient died from septicemia/neutropenic fever. Grade III-IV toxicities included anemia (9%), leukopenia (6%), thrombocytopenia (3%), renal toxicity (3%), headache (3%), fatigue (3%), nausea (3%), vomiting (3%), and alopecia (6%). CONCLUSIONS: TMZ combined with CDDP is an active and well-tolerated combination in patients with brain metastases from solid tumors.