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.     

Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.     

A complete response in squamous cell carcinoma of the lung to combination chemotherapy by cisplatin and vindesine

A 75-year-old male was admitted to our hospital for further investigation of a large mass shadow in the left hilum that was seen on an X-ray film of his chest. Cytological examination of his sputum revealed keratinized squamous cell carcinoma and combination chemotherapy using cisplatin and vindesine was administered. Later, both a chest X-ray and a CT scan showed a remarkable reduction in the size of the lung cancer. Complete response was obtained on the 90th hospital day, and was maintained with UFT administration. No sign of recurrence has been observed for over 9 months.     

Cisplatin, vindesine and bleomycin (CVB) combination chemotherapy of advanced non-small cell lung cancer

Fifty-four patients with advanced squamous, large-cell or adeno-carcinoma of the lung were treated with a three drug regimen of high-dose cisplatin, vindesine and a four-day bleomycin infusion (CVB). All patients had measurable disease; none had previously received chemotherapy. Of 52 patients evaluable for response, 20 (38%) had complete or partial remissions. The median duration of remission was 8 months (range, 6 1/2-19+ months), with eight patients continuing in remission. The median duration of survival for responding patients was 16 months versus five months for nonresponding patients (P greater than 0.001). Toxicity included mild to moderate myelosuppression, peripheral neuropathy, and nephrotoxicity, and was generally manageable. The addition of a four-day bleomycin infusion did not appear to offer a significant advantage over the combination of high-dose cisplatin and vindesine in the treatment of NSCLC. The response rate and survival duration produced by the CVB protocol were similar to those reported for the two-drug combination of vindesine and high-dose cisplatin.     

Neoadjuvant chemotherapy with carboplatin, ifosfamide, and peplomycin in advanced cervical squamous cell carcinoma

Background. To control advanced cervical squamous cell carcinoma more effectively and more easily, we used neoadjuvant chemotherapy, with three drugs carboplatin, ifosfamide, and peplomycin (PIP), in a study performed from July 1990 to October 1994 in nine Institutions. Methods. Sixty-five patients with untreated, inoperable squamous cell carcinoma of the cervix were treated with carboplatin (300 mg/m² IV; low-dose PIP regimen, or 400 mg/m² IV; high-dose PIP regimen) on day 1, ifosfamide (1000 mg/m², IV) on days 1–3, and peplomycin (5 mg/body, IM) on days 1–6. The low-dose PIP was given between July 1990 and April 1992, and the high-dose PIP from May 1992 to October 1994. Results. Response rates for the low- and high-dose PIP regimens were 42.9% (12/28) and 59.5% (22/37), respectively. Measurable lesions were recognized in the cervix, pelvic lymph node (PeN), paraaortic lymph node (PAN), lung, and supraclavicular lymph node. Response rates in these individual lesions to our low- and high-dose PIP regimens were 35.7% (10/28) and 55.6% (20/36), respectively in the cervical lesion and more than 50% for both regimens in the PeN and PAN metastatic lesions, while the supraclavicular lymph node metastatic lesions responded poorly to both regimens. After low-dose PIP, surgery was performed in 2 patients (2/28; 7.1%), while after high-dose PIP, 12 patients (12/37; 32.4%) underwent surgery. The 3-year survival rate of patients with high-dose PIP was significantly higher than that of those with low-dose PIP (P < 0.01). Conclusions. Neoadjuvant chemotherapy with PIP appears feasible and effective. The link between dosage and treatment response and achievable surgery rate and survival rates suggests that results might be further optimized by considering patients' renal function, and utilizing the Calvert formula for dosing analysis. Received: January 21, 1999 / Accepted: July 28, 1999     

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.     

Bleomycin-adriamycin combination chemotherapy in squamous cell carcinoma of the lung

A combination chemotherapy of bleomycin and adriamycin had been carried out in 12 male patients with squamous cell carcinoma of the lung, ranging from 47 to 80 years of age, and were inoperable because of the advanced disease. The method of drugs administration was as follows: Bleomycin was given at a dose of 15 mg by i.v. infusion twice weekly for the first two weeks, and once weekly thereafter until the cumulative dose reached 200 to 300 mg, provided severe toxicity such as pulmonary fibrosis was clinically or roentogenologically proved. Adriamycin was given at a dose of 20mg also by i.v. push twice weekly for the first two weeks, and the same procedure was repeated after a rest period of two to three weeks, until the dose reached nearly approximately a total dose of 200mg if no evidence of cardiotoxicity was observed and bone marrow suppression was negligible. Five cases out of twelve responded well to our bleomycin-adriamycin combination chemotherapy, demonstrating regression of the tumors in 50% or more, although two cases out of these five the responders were treated with radiation additionally. The median survival time of these responders was prolonged as long as 43 weeks, which was considered undoubtedly as favorable outcome, comparing with other clinical reports by others, even though the number of the cases in our clinical trial was rather small.     

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.     

Cisplatin, etoposide, ifosfamide, vincristine and bleomycin combination chemotherapy for far advanced testicular carcinoma.

Forty-eight patients with advanced testicular cancer, defined as abdominal mass greater than 10 cm, mediastinal mass greater than 5 cm, more than 20 lung metastases, or visceral organ involvement were treated with an intensive, alternating five-drug regimen consisting of cisplatin 50 mg/m2 d 1-3, etoposide 170 mg/m2 d 1-3, ifosfamide 5 g/m2 d 15, vincristine 2 mg weekly, bleomycin 15 mg/m2 weekly, q d 28. Thirty-four (71%) of the patients attained tumor-free status. This was achieved by chemotherapy alone in 14 patients and by surgical resection of residual disease in the remaining 20 patients (histology of resected tissue: necrosis 12, mature teratoma 7, viable carcinoma 1). Patients with pure seminoma responded better than patients with nonseminoma (CR 100% vs. 67%, respectively). In a univariate analysis only the value of HCG (less than vs greater than 10,000 U/L) and the number of involved organ sites (less than or equal to 2 vs greater than to 2) had significant influence on the response rate. After a minimum follow-up of 24 months 3 patients (9%) have relapsed. The survival rate is 76% after 36 months, with 61% remaining disease-free. Though this intensive regimen might bestow some of the therapeutic advantages of standard three-drug protocols in far advanced testicular cancer, the results are still less than optimal and warrant the exploration of new therapeutic strategies.     

Cisplatin and 5-fluorouracil chemotherapy in advanced or recurrent squamous cell carcinoma of the head and neck

Fifty-three patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with bolus cisplatin (CDDP) and 96-hour infusion of 5-fluorouracil (5-FU). Twenty-six patients with advanced disease (21 T4 and/or N3) and no prior therapy (NPT) received 2 to 3 cycles of chemotherapy prior to surgery and/or radiation. There were four complete responses (CR) and 12 partial responses (PR) to chemotherapy for an overall response rate of 61%. In 20 patients with locally recurrent or disseminated disease there was one CR and six PR for an overall response rate of 35%. All but one responding patient in both groups showed clear evidence of tumor response after the initial cycle of chemotherapy. Two of the five complete responders required at least three courses to achieve CR. Disease-free survival was poor: only five of 26 patients in the NPT group remain alive and free of disease 8 to 28 months from initial therapy. CDDP and 5-FU is an active combination for SCCHN, but survival benefit remains to be proven.     

Cisplatin and vindesine combination chemotherapy for non-small cell lung cancer: a randomized trial comparing two dosages of cisplatin

Forty-five patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2 every week) plus either high-dose cisplatin (120 mg/m2 every 4 weeks) or low-dose cisplatin (80 mg/m2 every 3 weeks). All patients were previously untreated. The response rate for the high-dose regimen of cisplatin was 39% (9/23) and that for the low-dose regimen of cisplatin was 33% (7/21); the difference was not statistically significant. Only one patient treated with high-dose cisplatin achieved complete response, lasting 6.5 months. The median duration of response was 5.6 months (range, 2.7-7.7) in the high-dose cisplatin group and 6.8 months (range, 1.9-8.9) in the low-dose cisplatin group. The median survival times for the 23 patients treated with the high-dose regimen of cisplatin and for the 21 patients treated with the low-dose regimen of cisplatin were 9.0 and 10.8 months, respectively. Significantly more azotemia occurred in the high-dose cisplatin group than in the low-dose cisplatin group (P less than 0.05). Combination chemotherapy with cisplatin and vindesine showed significant antitumor activity in patients with non-small cell lung cancer. However, the high-dose regimen of cisplatin did not result in a significantly better response rate or survival advantage, and was associated with greater toxicity.     

丝裂霉素、异环磷酰胺和顺铂治疗晚期非小细胞肺癌

目的 观察丝裂霉素、异环磷酰胺和顺铂组成的ＭＩＰ方案治疗晚期非小细胞肺癌的近期疗效,耐受性和生存期。方法 ５６例晚期非小细胞肺癌接受ＭＩＰ方案治疗。结果 可评价疗效病例５６例,总有效率４６．４％,中位缓解期８个月,中位生存期９．６个月,１年生存率３５．０％。主要毒副作用为骨髓抑制。;结论 ＭＩＰ联合化疗方案对晚期非小细胞肺癌有较好疗效,毒副作用可耐受。     

A case of advanced ureteral squamous cell carcinoma showing complete response to combination chemotherapy with cisplatinum, vindesine, and bleomycin]

A 56-year-old Japanese female was diagnosed as advanced squamous cell carcinoma of the left ureter, stage IV (T4N0M0), and treated with anti-cancer drugs using cis-platinum, vindesine, and bleomycin. The tumor vanished after the treatment. The specimen after left total nephroureterectomy and hysterectomy showed only granulomatous change with necrosis and foreign giant cells but not cancer cells.     

空洞型肺鳞癌与非空洞型肺鳞癌的临床特征分析

Objective： To identify the differences between cavitating squamous cell lung carcinoma （cSLC） and non-cavitating squamous cell lung carcinoma （ncSLC）. Methods： Fifty-one patients with cSLC and 281 with ncSLC confirmed by surgery in our hospital between 1999 to 2000 were collected and their clinical, histological and survival features were retrospectively ana（yzed. Results： Patients with cSLC had more frequent manifestation of infection and weight loss. They usually experienced longer duration of pre-diagnosis and showed bigger tumor mass, larger primary tumor invasion with worse differentiated than ncSLC patients. There was no significant difference in age, sex, smoking history, family tumor history, personal tuberculosis history, disease location, TNM stage, lymph node invasion, and metastasis between the two groups. Median survival time was 29 months for cSLC and 35 months for ncSLC. One- and 3- year survival rates were 86.3% and 43.1% for cSLC vs. 91.1% and 47,0% for ncSLC respectively （P〉0.05）. Conclusion： Patients with cSLC presented with a bigger mass, a larger extent of primary tumor invasion, worse differentiated, more obstructed pneumonia that might result in longer duration of pre-diagnosis and more weight loss. As lack of differences in disease stages, lymph node invasion, metastasis and especially survival time with ncSLC, cSLC couldn＇t be classified as a special type of squamous cell carcinoma by present evidences.     

Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma.

Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.     

Cisplatin, etoposide, and ifosfamide in non-small cell lung carcinoma. A phase II randomized study with cisplatin and etoposide as the control arm

A Phase II randomized study testing the combination of cisplatin, etoposide, and ifosfamide (PEI) in non-small cell lung cancer (NSCLC) was performed. The standard combination of cisplatin and etoposide (PE) was used as the control arm. Since January 1987, 78 patients were enrolled and then stratified for previous treatments and performance status (PS). The response rate (RR) of PEI was 26% (95% confidence limits [95 CL], 12% to 40%), with one complete response (CR). The RR of PE was 26% (95 CL, 13% to 39%), with no CR. The median response duration was 5 months (range, 2 to 13 months) for PEI and 4 months (range, 2 to 6 months) for PE. The median survival time was 6 months (range, 1 to 22+ months) for PEI and 7 months (range, 1 to 21+ months) for PE. Leukopenia at recycling was similar in both arms (25% for PEI and 29% of PE). The median leukocyte nadir was 2100/microliters (range, 430 to 4870/microliters) for PEI patients and 3150/microliters (range, 500 to 5000/microliters) for PE patients. Three patients had a drug-related death secondary to infections. This Phase II randomized study suggested that the combination of cisplatin plus etoposide and ifosfamide produces results similar to those obtainable with cisplatin and etoposide.     

VIP与MVP方案治疗非小细胞肺癌的对照研究

目的:通过前瞻性对照研究,比较VIP方案与MVP方案治疗晚期非小细胞肺癌的疗效及不良反应.方法:共53例晚期的非小细胞肺癌患者随机入组,治疗组应用VIP方案(VDS+IFO+DDP),对照组应用MVP方案(MMC+VDS+DDP),每例病人至少化疗2疗程.疗效及不良反应评价均按WHO标准进行,每例病人随访生存期.结果:治疗组中1例CR,15例PR,8例SD,1例PD,有效率(CR+PR)为64.0%;对照组中11例PR,11例SD,6例PD,有效率(CR+PR)为39.3%.治疗组有效率比对照组高,但无统计学差异(P=0.072).治疗组中位生存期为8个月,而对照组为7月,两组无差异(P>0.05),该组资料目前仍在继续进行随访.两组不良反应均主要为骨髓抑制、恶心呕吐、脱发.Ⅲ+Ⅳ的血白细胞下降治疗组为56.0%,对照组为50.0%,两组无差异(P>0.05).结论:初步的结果显示VIP方案对于非小细胞肺癌的有效性较高,可以作为一线方案在临床使用.     

异环磷酰胺联合奈达铂与单药多西他赛二线治疗晚期肺鳞癌的临床比较

目的　比较国产异环磷酰胺（ＩＦＯ）联合奈达铂（ＮＤＰ）与单药多西他赛（ＴＸＴ）二线治疗晚期肺鳞癌的疗效、毒副反应及预后。方法　回顾性分析我院接受二线化疗的７７例晚期肺鳞癌患者的临床资料,３７例接受ＩＦＯ联合ＮＤＰ治疗(联合组）,４０例接受单药ＴＸＴ治疗（单药组）。具体用药如下：ＩＦＯ１.３ｇ／ｍ^２,ｄ_１ ～ｄ_３;ＮＤＰ８０～１００ｍｇ／ｍ^２,ｄ_１;ＴＸＴ７５ｍｇ／ｍ^２,ｄ_１。均２１天为１周期,２周期评价疗效和毒副反应。结果　联合组客观有效率（ＲＲ）为４０.５％,单药组ＲＲ为１７.５％,两组差异具有统计学意义（Ｐ＜０.０５）;联合组疾病控制率（ＤＣＲ）为８６.５％,单药组ＤＣＲ为７５.０％。联合组１年生存率为３２.１％,中位总生存期（ＯＳ）为１０.０个月,单药组１年生存率为２９.２％,中位ＯＳ为９.０个月,两组差异无统计学意义（Ｐ＞０.０５）;联合组中位无进展生存期（ＰＦＳ）为１８.０周,单药组中位ＰＦＳ为１３.０周,两组差异有统计学意义（Ｐ＜０.０５）。联合组的毒副反应包括白细胞减少、血小板减少及恶心、呕吐,发生率均明显高于单药组。经Ｃｏｘ多元回归分析,治疗前ＰＳ评分、肿瘤分期及二线治疗获益情况均为影响患者生存的独立预后因素。结论　ＩＦＯ联合ＮＤＰ方案较单药ＴＸＴ二线治疗晚期肺鳞癌患者未显著增加患者的ＯＳ,但近期有效率更高,并能延长患者的ＰＦＳ;血液学及消化道毒副反应更明显,但可耐受。     

Nuclear DNA content in squamous cell carcinoma, small cell carcinoma, and bronchiolo-alveolar carcinoma of the lung

Nuclear DNA content in individual, morphologically identified tumor cells from 33 squamous lung carcinomas, 20 small cell lung carcinomas, and 10 bronchiolo-alveolar carcinomas were analyzed by means of cytophotometry on Feulgen-stained histologic and cytologic specimens. Twenty-eight of the squamous cell carcinomas and 17 of the small cell carcinomas had high and scattered DNA values, indicative of high malignancy potentials. None of the bronchiolo-alveolar carcinomas showed such high DNA values. These results are in line with clinical experience that squamous cell and small cell carcinoma are associated with rapid progression and death in patients, whereas bronchiolo-alveolar carcinomas have a more indolent course.