Use of cisplatin, cyclophosphamide, vincristine, and doxorubicin for the treatment of non-small cell lung cancer

Forty-four evaluable patients with non-small cell carcinoma of the lung were treated with cisplatin, cyclophosphamide, vincristine, and doxorubicin. The overall response rate was 57%. The 16% who had complete response had a median survival of 81 weeks.     

Phase II trials of 5-FU, doxorubicin, and cisplatin in advanced, measurable adenocarcinoma of the lung and stomach

A combination of 5-FU (600 mg/m2 on Days 1 and 8), doxorubicin (40 mg/m2 on Day 1), and cisplatin (75 mg/m2 on Day 1) has been used for treatment of 31 patients with advanced measurable adenocarcinoma of the lung and 35 with gastric cancer. The regimen was given every 4 weeks until disease progression to patients who had not received prior chemotherapy. One complete response occurred in the lung cancer group. Ten of the gastric cancer patients (29%) had partial responses. The median duration of response was 5.5 months and the median survival in responding patients was 10.8 months. Toxicity of the regimen was moderate. We conclude that this combination offers no particular advantages over previously described treatments for these diseases.     

Cisplatin, doxorubicin, and cyclophosphamide chemotherapy for advanced endometrial carcinoma

Nine of 19 patients (47%) with widespread or recurrent endometrial carcinoma responded to chemotherapy with cisplatin, doxorubicin, and cyclophosphamide. Two complete clinical responses and seven partial responses were achieved. A "second-look" laparotomy documented the complete response in one patient. The addition of cisplatin to doxorubicin and cyclophosphamide increased toxicity without increasing the antitumor activity previously reported for the two-drug combination. Performance status had a marked influence on response, while sites of metastases, amount of residual disease, and histologic grade did not affect the response rate. A schema for the treatment of patients with endometrial carcinoma with progestins and/or cytotoxic chemotherapy is suggested.     

Comparison of cyclophosphamide plus cisplatin versus hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin in combination as initial chemotherapy for stage III and IV ovarian carcinomas

Among 187 women with stage III and IV ovarian carcinoma who participated in this comparative clinical trial, 181 were eligible for analysis. Of these patients, 89 received monthly treatment with CP [cyclophosphamide (1 g/m2) plus cisplatin (60 mg/m2)] and 92 received monthly treatment with HCAP [hexamethylmelamine (150 mg/m2/day X 7), cyclophosphamide (400 mg/m2), doxorubicin (30 mg/m2), and cisplatin (60 mg/m2)]. All treatments were administered iv on Day 1 of each monthly treatment cycle, except for hexamethylmelamine, which was administered orally on Days 2-8. With a median follow-up time of 30 months, survival curves for the two treatment groups were almost identical, as were their times to progression [estimated median survival, 24.6 months (Kaplan-Meier)]. Patient characteristics which significantly influenced survival were age, degree of histologic differentiation, extent of residual disease, stage of disease, and histologic type. Results of posttreatment laparotomies have been equal for the two treatment groups. Toxic effects of the two regimens have been similar, except for more frequent, more severe, and earlier neurotoxicity among patients treated with HCAP. Of the two regimens, CP has the better therapeutic index.     

Cyclic chemotherapy with cyclophosphamide, doxorubicin, and cisplatin plus vinblastine and bleomycin in advanced germinal tumors. Results with 100 patients

One hundred patients with advanced mixed germ-cell tumors were treated with cisplatin, cyclophosphamide, and doxorubicin alternating with vinblastine and bleomycin (cyclic CISCAII/VBIV). The chemotherapy achieved an 89 percent continuous disease-free status (85 percent with chemotherapy, 4 percent with chemotherapy plus surgery). The mean follow-up duration for patients with continuous complete remission was 132 weeks (+/- 6.2), with a median of 126 weeks. Multivariate analysis using a stepwise logistic regression of prognostic variables revealed that a high serum level of the beta subunit of human chorionic gonadotropin (more than 50,000 mIU/ml) was of prognostic significance, followed by the Samuels staging criteria and extragonadal origin of disease. Thirty-two patients underwent exploratory surgery after they had had two courses of chemotherapy beyond the establishment of a stable mass and absent serum biomarkers. No viable cancer was found at exploration, and all patients remain alive and free of disease. The acute toxicity of the cyclic chemotherapy was formidable, but only one patient had a fatal complication. Thirty-six percent of the CISCAII courses and 44 percent of the VBIV courses were associated with leukopenic fever, and 5 percent of the CISCAII courses and 8 percent of the VBIV courses were associated with culture-positive infection. Long-term toxicity was unusual: bleomycin lung toxicity 1 percent, cardiac toxicity 1 percent. CISCAII/VBIV cyclic chemotherapy is superior to cisplatin, vinblastine, and bleomycin (PVB) chemotherapy; it results in a higher complete remission rate, a lower relapse rate, and a lower incidence of long-term complications. Patients with a high risk of failure of PVB chemotherapy (Samuels stage IIIB3 to IIIB5) or with extragonadal tumors should be treated with CISCAII/VBIV.     

Etoposide,doxorubicin (Adriamycin) and cisplatin regimen in advanced gastric adenocarcinoma: experience with a lower dose schedule

A phase II trial of etoposide (100 mg/m²) on days 4, 5, 6, doxorubicin (Adriamycin, 20 mg/m²) on days 1, 7, and cisplatin (30 mg/m²) on days 2, 8 (EAP) was carried out in order to reduce toxicity associated with a full-dose EAP regimen for advanced and/or metastatic gastric adenocarcinoma. Out of 21 evaluable patients, 2 (10%) had a complete response (CR), 7 (33%) had a partial response (PR), 4 (20%) showed no change and 8 progressed (38%). The mean duration of response (CR+PR) was 8.4+ months. Survival of the whole group was 7.5+ months. Treatment was quite well tolerated by most patients on an outpatient basis. Grade 3 vomiting and leukopenia were seen in 30% and 35% of cases respectively. One patient had grade 3 esophagitis, and 1 patient was hospitalized for severe grade 4 febrile leukopenia. Although the EAP regimen cannot be considered a standard therapy for gastric cancer, the EAP schedule employed in this study seems to be better tolerated than those reported by other authors, and can sefely be given on an outpatient basis.     

Combination chemotherapy for advanced ovarian cancer: a prospective randomized trial comparing hexamethylmelamine and cyclophosphamide to doxorubicin and cyclophosphamide

Forty-three patients with advanced stage III and IV epithelial cancers of the ovary were entered in a prospective randomized study comparing doxorubicin and cyclophosphamide to hexamethylmelamine and cyclophosphamide chemotherapy. No statistical difference in the overall response rates or survival times was demonstrated. However, the combination of doxorubicin and cyclophosphamide was more effective in inducing a response in histologically poorly differentiated cancers than in well-differentiated and moderately differentiated cancers, and the therapeutic implications of this observation are discussed.     

Cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin (CHAD) as second-line chemotherapy for ovarian adenocarcinoma

Twenty women with recurrent ovarian adenocarcinoma received a monthly four-drug combination of cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin as second-line chemotherapy. There were no objective responses to this regimen. This is in contrast to the 49% response rate reported by Kane et al using these four drugs and the 63% response rate reported by Vogl et al using three of these drugs as second-line chemotherapy. The differences in the three regimens are reviewed; however, we could not identify reasons sufficient to account for the disparity in response rates.     

Combined intravenous and intra-arterial cyclophosphamide, doxorubicin, and cisplatin (CISCA) in the management of select patients with invasive urothelial tumors

Twenty-eight patients with unresectable urothelial tumors who had no evidence of distant visceral metastasis were managed with iv CISCA (cyclophosphamide, doxorubicin, and cisplatin) and intra-arterial (ia) CISCA chemotherapy. Ten patients had locally advanced disease only and 18 had locally advanced disease with nodal metastasis (ten in pelvic nodes; seven in pelvic and para-aortic nodes; and one in pelvic, para-aortic, and mesenteric nodes). Eleven patients (39%) achieved a complete remission, with a median duration of 49 weeks (range, 25-108). Seven patients (25%) achieved on objective response and ten patients (36%) failed to respond. Iv and ia CISCA chemotherapy is effective in the management of advanced urothelial tumors. Patients with locally advanced disease with or without the presence of nodal metastasis are a select population in whom frequent complete remissions can be achieved.     

含羟基喜树碱的序贯化疗方案治疗中、晚期胃癌的初步探讨

目的：观察甲酰甲氢叶酸钙（LV）、较小剂量氟尿嘧啶（5－Fu)与顺铂（DDP）加羟基喜树碱（HCPT）组成的FDH方案序贯给药,治疗中、晚期胃癌的临床疗效。方法：治疗组23例,给予FDH方案;对照组30例,用5－Fu、阿霉素（Ara-c)和丝裂霉素组成的FAM方案。两个方案以均时间先后顺序给药。FDH方案为LV 100mg/d,静脉注射,30min内滴完;5－Fu500mg/m^2静脉滴注,持续8h,第1－5天;顺铂10mg/m^2静脉注射,第1－5天;HCPT 10mg/m^2静脉滴注1h,第1－5天,每月为1个疗程。FAM方案为LV 100mg/d,静脉注射,30min内滴完;5－Fu750－1000mg/m^2静脉滴注第1－天;阿霉素30mg/m^2静脉注射,第1天,丝裂霉素6mg/m^2静脉注射,第1天,每月为1个疗程。每例至少用完2个疗程,方可评价疗效。结果：FDH组23例中,完全缓解（CR）1例,部分缓解（PR）12例,稳定（NC）6例,进展（PD）4例,有效率为56．3％。FAM组30例,PR9例,NC13例,PD8例,有效率为33．3％,两组有效率比较,差异有显著性（P＜0．05）。两组主要不良反应均为白细胞减少和胃肠道反应,FDH组Ⅲ-Ⅳ度的白细胞下降（21．7％）按FAM组（46．4％）低（P＜0．05）,未见心、肾、膀胱炎等不良反应。结论：FDH方案治疗中、晚期胃癌疗效较好,不良反应少,值得临床进一步研究。     

Phase I study of docetaxel, cisplatin and concurrent radiotherapy for locally advanced gastric adenocarcinoma

This phase I study is designed to determine the maximal tolerated dose and the dose-limiting toxicity of docetaxel with cisplatin and concurrent radiotherapy in patients with unresectable locally advanced gastric adenocarcinoma. Docetaxel was given once a week with the dosage escalated from 5 mg/m(2) to 15 mg/m(2) in increments of 2.5 mg/m(2). Cisplatin were administered at 20 mg/m(2) once a week. Radiotherapy was delivered to 50.4Gy at 1.8Gy/day. At least three patients were enrolled at each level. The maximal tolerated dose (MTD) and dose-limiting toxicity (DLTs) was determined. The DLTs were defined as grade 3 or 4 hematologic and nonhematologic toxicity. Twenty-one patients with locally advanced gastric adenocarcinoma were enrolled. Grade 1-2 neutropenia and nausea/vomiting were the most common side effects. The first DLT (grade-3 neutropenia) was observed in one of three patients at 12.5 mg/m(2) docetaxel. Three more patients were enrolled, but DLT was not observed and 6 patients were enrolled into 15 mg/m(2) group, DLT occurred in 3 patients (1 Grade 3 neutropenia, 1 Grade 4 neutropenia and 1 Grade 3 nausea/vomiting). Overall tumor response rate was 66.7% with 28.6% complete and 38.1% partial response. In conclusion, the MTD of docetaxel was 15 mg/m(2), and the recommended dose of docetaxel for Phase II study was 12.5 mg/m(2) weekly. The docetaxel and cisplatin with concurrent radiotherapy were tolerable and feasible in treating locally advanced gastric adenocarcinoma.     

Efficacy and toxicity of fluorouracil, doxorubicin, and cisplatin/nedaplatin treatment as neoadjuvant chemotherapy for advanced esophageal carcinoma

OBJECTIVE: Patients with advanced esophageal carcinoma including clinical T4 tumor, extensive lymph node metastasis, or intramural metastasis have a dismal prognosis, despite recent multimodality treatments. The aim of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy using fluorouracil, doxorubicin, and cisplatin or nedaplatin (FAP/N) in these patients. MATERIAL AND METHODS: Twenty-six patients were enrolled in this study. The first 9 patients received 600 mg/m2 fluorouracil on days 1-7 and days 29-35, and 30 mg/m2 doxorubicin and 60 mg/m2 cisplatin on days 1 and 29 (FAP). The next 17 patients received modified FAP, in which 50 mg/m2 nedaplatin was given instead of cisplatin (FAN). RESULTS: Grade 3 or 4 toxicities developed in 6 patients (23.1%) during chemotherapy, but there was no discontinuation of treatment. The clinical response rate was 46.2%. Twenty-one patients (80.8%) underwent esophagectomy, and R0 resection was achieved in 16 patients (61.5%). The 1-year survival rates of 26 patients, 21 patients with resectable tumor, 16 with R0 resection, and 12 clinical responders, were 31.3%, 32.1%, 33.3%, and 45.5%, respectively, each with a median survival time of 9 months. The median progression-free survival time of 26 patients was 6 months; in 16 patients with R0 resection progression-free survival was 6.5 months. There was no correlation between the recurrence pattern and tumor spread before treatment. CONCLUSIONS: FAP/N was found to have acceptable toxicities and the ability to control locoregional tumors, but made little contribution to patient survival. The efficacy of this treatment for patients with advanced esophageal carcinoma, however, may not yet be apparent.     

Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial

To investigate the activity of etoposide, doxorubicin, and cisplatin plus mitotane in the management of advanced adrenocortical carcinoma (ACC) patients, 72 patients with measurable disease not amenable to radical surgery were enrolled in a prospective, multicenter phase II trial. EDP schedule (etoposide 100 mg/m(2) on days 5-7, doxorubicin 20 mg/m(2) on days 1 and 8, and cisplatin 40 mg/m(2) on days 1 and 9) was administered intravenously every 4 weeks. Concomitantly, patients were given up to 4 g/day of oral mitotane. Five patients achieved a complete response and 30 a partial response, for an overall response rate of 48.6% (95% CI: 37.1-60.3). Median time to progression in responding patients was 18 months. The EDP regimen was well tolerated, leukopenia being the dose limiting toxicity. One toxic related death due to septic shock, however, was registered. Radical surgical resection of residual disease after chemotherapy was performed in 10 patients. The overall survival of patients attaining a disease free status (clinical complete responders+radically resected) was significantly higher than that of patients with partial response or no response (P<0.002). Androgen secretion was associated with long survival, while glucocorticoid secretion was associated with poor prognosis both in univariate and multivariate analysis. In conclusion, EDP plus mitotane is an active and manageable combination scheme for ACC patients. Surgical resection of residual disease subsequent to chemotherapy leads to a more favourable outcome. The natural history of the disease is significantly influenced by the secretory status of the tumor.     

A combination immunochemotherapy of 5-fluorouracil, cisplatin, leucovorin, and OK-432 for advanced and recurrent gastric carcinoma

BACKGROUND/AIMS: Based on theories of biochemical modulation and immunotherapy, a novel regimen consisting of 5-fluorouracil, cisplatin, leucovorin, and OK-432 (FLPO therapy) was devised for the treatment of patients with advanced and recurrent gastric carcinoma. METHODOLOGY: The 14-day combination therapy consisted of continuous infusion of 5-fluorouracil (250 mg/m2/day), a bolus injection of 10 mg cisplatin and 30 mg leucovorin every other day, and a subcutaneous injection or per oral administration of OK-432 (3KE or 5KE) every other day. Thirty patients completed 59 courses of treatment consisting of 2 weeks of therapy followed by at least 2 weeks rest. RESULTS: The overall response rate was 40%, with 1 complete response and 11 partial responses observed. All twelve patients responded after 1 course of treatment. The response rate differed depending upon tumor location, 22.2% at the primary site, 60.0% in the lymph nodes, 45.5% with peritoneal dissemination, 44.4% with liver metastases, 50.0% in the lung, and 100.0% with skin metastases. The most frequently observed toxicity was stomatitis (53.3%). The overall incidence of toxicities of grade 3 or greater was 6.6%, including diarrhea (3.3%) and stomatitis (3.3%). One patient required treatment interruption because of the grade 3 toxicity of diarrhea. The median survival time was 198 days overall, 242 days for responders and 125 days for non-responders. CONCLUSIONS: FLPO therapy seemed to be an effective regimen for the treatment of advanced and recurrent gastric carcinoma.     

Successful use of cyclophosphamide, bortezomib, and dexamethasone to treat a case of relapsed POEMS

POEMS syndrome is a rare paraneoplastic condition related to myeloma. Because it is rare, there is very little known about treatment options. The use of potentially neurotoxic chemotherapeutic drugs is of concern in a disease whose major manifestation is neuropathy. Herein, we describe an extraordinary response to the combination of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in a patient with relapsed, life-threatening POEMS syndrome.