Combination chemotherapy with cisplatin, bleomycin, and methotrexate in patients with advanced head and neck cancer

Twenty-six patients with advanced head and neck cancer, 22 of whom had failed prior surgery and/or radiotherapy, were treated with a combination regimen of cis-diamminedichloroplatinum II, bleomycin, and methotrexate. There were no complete responses. Nine patients achieved a partial response (35%). Three of the four (75%) patients without prior therapy achieved a partial response while only 6 of the 22 patients (27%) with prior surgery and/or radiation therapy obtained a partial response. The median response duration was 3 months. Patients with a partial response did not live significantly longer than those who did not live significantly longer than those who did not respond. Toxic reactions were frequent: there were three episodes of sepsis secondary to leukopenia and two cases of bleomycin pulmonary toxicity. Mucositis was noted in 40% and nausea and vomiting in 60% of patients. We conclude that this triple-drug regimen has little value in the treatment of patients with advanced squamous cell carcinoma of the head and neck who have failed prior surgery and radiotherapy.     

No correlation between response and survival in patients with multiple myeloma treated with vincristine, melphalan, cyclophosphamide, and prednisone

A vincristine, melphalan, cyclophosphamide, and prednisone (VMCP) multi-drug regimen was used in 85 previously untreated patients with multiple myeloma (MM) (symptomatic Durie Stages II and III) until they became refractory. The prognostic significance of various pretreatment characteristics was evaluated in terms of therapeutic response (according to Southwest Oncology Group [SWOG] and Chronic Leukemia-Myeloma Task Force [TF] criteria) and survival. Therapeutic responses, obtained in 31.2% (SWOG) and 68.7% (TF) of patients, had a significant inverse correlation with myeloma cell mass, serum calcium, and bone status. Median survival time of Stage II and Stage III patients was 39 and 34 months, respectively. Serum B2 microglobulin greater than or equal to 6 micrograms/ml was the only variable correlating unfavorably with survival duration after multi-variate analysis (increased risk = 2.79), although therapeutic response as a time-dependent variable had no effect on survival. These data suggest no correlation between response and survival, partially because of inadequate response assessment criteria and partially because no existing treatment is curative (although current therapeutic approaches may prevent death from complications).     

Pilot study with cisplatin, ifosfamide, and etoposide in advanced non-small-cell lung carcinoma

Twenty-five patients with advanced non-small-cell lung carcinoma (NSCLC) were treated with a multidrug regimen (CIV) consisting of ifosfamide (IFX), cisplatin (CDDP), and etoposide (VP-16). Twenty-four patients were evaluable for response. An objective response was detected in eight cases (33%), including one case with complete tumor response. Median duration of response was 31 weeks, and median overall survival 46 weeks, with no significant difference between responders and nonresponders. Myelosuppression and gastrointestinal side effects represented the main toxic manifestations; a toxic death and an ischemic cardiac episode were also observed. CIV seems a moderately effective regimen in NSCLC, but unlikely to provide an advantage over the widely employed two-drug combination of CDDP and VP-16.     

Correlation between HER-2 expression and response to neoadjuvant chemotherapy with 5-fluorouracil,doxorubicin, and cyclophosphamide in patients with breast carcinoma

BACKGROUND: The objective of this study was to determine whether HER-2 overexpression is associated with improved response to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) in patients with breast carcinoma. METHODS: Ninety-seven patients with Stage I-III breast carcinoma were included. HER-2 expression was determined by routine clinical laboratory assessment, and tumors with 3 + immunohistochemistry staining intensity or gene amplification by fluorescent in situ hybridization were considered HER-2 positive. Response was assessed by physical examination, imaging assessment, and pathologic assessment at the time of surgery. RESULTS: The median patient age was 45 years. At baseline, 68% of patients had lymph node positive disease, 87% had >/= T2 tumors, and 28% of patients had HER-2 positive tumors. Eighty-four percent of patients received four courses of FAC, 8% of patients received 3 courses of FAC, and the remaining 8% of patients received 5-6 courses of FAC. The clinical response rate (complete response [CR] and partial response [PR]) was 78%, the imaging response rate (CR and PR) was 64%, and 15% of patients had a good pathologic response, defined as a CR or minimal residual disease (tumor measuring < 1 cm in greatest dimension and negative lymph nodes). Concordance between the three methods of response assessment (clinical, pathologic, and imaging) was modest and was best between clinical assessment and imaging assessment (64% concordance). HER-2 status did not correlate with pathologic or clinical response (assessed by physical examination or imaging), although a nonsignificant trend was noted toward better response in patients with breast tumors that overexpressed HER-2. CONCLUSIONS: The authors found no significant correlation between HER-2 expression and clinical or pathologic response to neoadjuvant chemotherapy in patients with breast carcinoma.     

Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas.

From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.     

Prospective randomized trial in advanced malignant melanoma with cis-platinum, vindesine, and etoposide vs. cis-platinum, vindesine, and lomustine

Thirty-seven consecutive patients with disseminated malignant melanoma and previously untreated with chemotherapy were randomly allocated to receive vindesine, cis-platinum, and etoposide (Regimen A) or vindesine, cis-platinum, and lomustine (Regimen B). In 31 evaluable patients, Regimen A induced an overall response rate of 31% and a complete response rate of 6%; with Regimen B the corresponding findings were 20% and 20%, respectively. The median duration of complete response was 12 months with both regimens and the comparative median total survivals were 8 and 6 months, respectively. In no case was toxicity so severe to require treatment discontinuation, and the major dose-limiting side effect was myelosuppression, especially in the patients treated with Regimen B. Present results confirm once more the limited activity of drugs and regimens presently utilized in the treatment of advanced malignant melanoma.     

A randomized study comparing platinum, doxorubicin, and VP-16 with platinum, 4'-epidoxorubicin, and VP-16 in patients with non-small-cell lung cancer

Forty-four previously untreated patients with advanced non-small-cell lung cancer were treated in a randomized trial comparing platinum (60 mg/m2), doxorubicin (40 mg/m2), and VP-16 (150 mg/m2) (PAV) with platinum (60 mg/m2), 4'-epidoxorubicin (50 mg/m2), and VP-16 (150 mg/m2) (PEV). The overall response rate was 10%. Major response rates were quite similar for the 21 patients treated with PAV (5%) and the 23 patients treated with PEV (18%) (p = 0.2). Of the 23 patients with assigned to PEV, two (9%) achieved complete responses for a median duration of 20 weeks and 44+ weeks. There was no significant difference (p = 0.75) in the median survival among patients treated with PAV (24 weeks) and those treated with PEV (20 weeks). Toxicity was generally mild and tolerable. The lack of response found in both arms of treatment caused the study to be terminated early. Some benefit could be appreciated in patients with limited disease and good Karnofsky performance status.     

Neoadjuvant chemotherapy with cyclophosphamide, mitoxantrone, and 5-fluorouracil in locally advanced breast cancer

OBJECTIVES: Our primary objective was to determine the response rate; secondary objectives were to assess the toxicity rate, and disease-free and overall survival rates in patients with locally advanced breast cancer (LABC) receiving a cyclophosphamide (500 mg/m2), mitoxantrone (12 mg/m2) and 5-fluorouracil (500 mg/m2) (CMF) chemotherapy regimen. PATIENTS AND METHODS: The data from 74 patients with LABC with neoadjuvant CMF chemotherapy were analyzed retrospectively. Preoperatively, all patients received 3 cycles of CMF on day 1, repeated every 21 days. In 3 (4.1%) patients, breast-conserving surgery was given and in 71 (95.9%) modified radical mastectomy. All patients received radiotherapy and 3 additional cycles of CMF chemotherapy after surgery. RESULTS: Median age of the patients was 47 years (range: 17-74). 43 patients were premenopausal, whereas 31 were postmenopausal. 54 patients were in stage IIIA, and 20 were in stage IIIB. The overall clinical response rate was 88%; 11 (14.9%) had a complete response, 54 (73%) had a partial response, and 2 (2.8%) had progression. 14 (18.9%) had a pathological complete response. The median follow-up was 62 months. The median disease-free survival was 64.9 months, and the median overall survival was 97.5 months. The 5-year disease-free and overall survival rates were 52% and 79.9%, respectively. Most frequent side-effects were nausea/vomiting, mucositis, alopecia and leukopenia. CONCLUSION: The CMF regimen has a high overall response rate and an acceptable side effect profile in the treatment of locally advanced breast cancer. Further studies are needed to evaluate its effectiveness in breast-conserving strategies.     

Phase II study of combination therapy with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small-cell lung cancer.

Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.     

Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse

BACKGROUND: The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse. METHODS: Patients received topotecan (2.4 mg/m(2) daily as a 30-minute infusion) for 5 days before induction therapy with dexamethasone, vincristine, and asparaginase (native or pegylated Escherichia coli). The pharmacokinetics of topotecan were measured with the first dose of treatment in 23 patients. RESULTS: Twenty-eight of 31 patients with circulating blast cells were evaluable for response to topotecan. Twenty-five patients (89.3%) had a response (>25% decrease in circulating blast cells). The leukocyte count (P = .0001) and blast cell count (P = .0009) declined significantly during topotecan therapy. The median (range) topotecan lactone area under the concentration-time curve after the first dose was 85.4 L/hour/m(2) (range, 38.7-229.3 L/hour/m(2)). At the end of induction, 23 patients (74.2%) had a complete response, 1 patient (3.2%) had a partial response, 5 patients (16.1%) had no response, and 2 patients had died of infection. Six of the 17 patients who were studied for minimal residual disease (MRD) achieved MRD-negative status at the end of induction. The main toxicities were hematologic, gastrointestinal, and hepatic. The estimated 5-year survival rate, event-free survival rate, and cumulative incidence of second relapse were 24.1% +/- 7.9%, 18.2% +/- 7.4%, and 22.8% +/- 8.7%, respectively, in the 29 patients who had a hematologic first relapse. CONCLUSIONS: A regimen comprising single-agent topotecan given with a standard 3-drug combination was effective in inducing remission in pediatric patients with relapsed ALL and was tolerated well.     

Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines

BACKGROUND: To assess the efficacy and safety of the combination of non-pegylated liposome-encapsulated doxorubicin (Myocet(R)) with cyclophosphamide, vincristine, prednisone and rituximab (R-COMP) in patients with aggressive non-Hodgkin's B-cell lymphomas. METHODS: Twenty-one patients were selected for the presence of negative concurrent clinical features such as cardiac comorbidity and/or previous treatment with anthracycline-based regimens. Liposome-encapsulated doxorubicin at a dose of 50 mg/m(2) was administered in association with cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), prednisone (40 mg/m(2)) and rituximab (375 mg/m(2)) every 21 days for four to six cycles unless progression or unacceptable toxicity occurred. RESULTS: A complete response (CR) was obtained in 16/21 patients (76%), three patients achieved a partial response (14%), with an overall response rate of 90%. Two patients (10%) did not respond to therapy. After a median follow-up of 13 months (range 2-36 months), 2/16 CR patients relapsed, with a disease-free survival (DFS) of 78%. CONCLUSIONS: The replacement of doxorubicin with its non-pegylated liposomal pharmaceutical analogue was well tolerated and highly effective in inducing remission in this group of patients at high risk for cardiac toxicity or previously treated with anthracyclines. Its high tolerability and low incidence of cardiac events (only one patient) warrants further studies to confirm the clinical benefits of liposomal doxorubicin in this subset of patients.     

环磷酰胺等6种药物联合治疗34例晚期乳腺癌

目的：观察环磷酰胺、甲氨蝶呤、氟尿嘧啶、平阳毒素、顺氯氨铂、强的松联合（CMFBDP方案）治疗晚期乳腺癌的疗效和毒副反应。方法：34例临床Ⅲ、Ⅳ期乳腺癌患者行CMFBDP联合方案为主的治疗。结果：初治组有效率80%，复治组有效率65.5%。毒副反应主要为恶心呕吐。结论：CMFBDP联合化疗方案治疗晚期乳腺癌是有效和安全的。     

Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma.

BACKGROUND: This Phase II study was undertaken to assess the efficacy and toxicity of chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone (EPOCH regimen) in patients with advanced, refractory cutaneous T-cell lymphoma (CTCL). METHODS: Fifteen patients were treated with a 96-hour continuous infusion of etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone, followed by granulocyte-colony stimulating factor support and trimethoprim/sulfamethoxazole prophylaxis. The median age of the patients was 53 years (range, 17-82 years). Six patients had Sézary syndrome (SS), four patients had visceral involvement, and four patients had anaplastic large cell morphology, three with Ki-1 (CD30) positivity. All patients had disease that was refractory to prior chemotherapy or electron beam irradiation and eight of these patients had received cyclophosphamide, doxorubicin, vincristine, and prednisone. Seven patients had received prior interferon therapy and nine patients had received fludarabine and/or 2-CDA. RESULTS: After a median of 5 cycles (range, 1-9 cycles), 4 patients achieved a complete response (27%) and 8 patients achieved a partial response (53%) for an overall response rate of 80% (95% confidence interval, 52-96%). Three patients with visceral involvement, two of three patients with anaplastic large cell morphology, and one patient with human T-cell lymphoma virus leukemia/lymphoma did not respond. All 12 responders had improvement in skin disease; 2 of 6 patients with SS had complete disappearance of circulating Sézary cells. The median progression free survival was 8.0 months (range, 3-22 months). After a median follow-up of 11.4 months (range, 2-56+ months), the median patient survival was 13.5 months. Grade 3 or 4 hematologic toxicity occurred in 8 patients (61%); 5 of these 8 patients had febrile neutropenia. Six patients developed staphylococcal bacteremia, two patients had disseminated herpes infection, and one patient had Pneumocystis carinii pneumonia. Grade 3 neurotoxicity occurred in one patient. Two patients had a significant decrease in left ventricular ejection fraction and one patient had supraventricular tachycardia. CONCLUSIONS: EPOCH chemotherapy has a high response rate with acceptable toxicity in patients with advanced and refractory CTCL.     

Combination chemotherapy with 5-fluorouracil, CCNU, and vincristine in metastatic colorectal carcinoma

Twenty-four patients with metastatic colorectal carcinoma were treated with a chemotherapeutic regimen consisting of 5-fluorouracil, CCNU, and vincristine (FCV). Twenty patients were evaluable for response and 22 were evaluable for drug toxicity. One patient (5%) showed partial response, eight patients (40%) had stabilization of disease, and the remaining 11 patients (55%) had progression of disease. There was no statistically significant difference between the median survivals of patients with stabilization and of those with progression of their disease (p greater than 0.01). We were unable to demonstrate objective efficacy of the FCV regimen in the schedule used.     

Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia

BACKGROUND: The prevalence of chronic lymphocytic leukemia (CLL) increases with age. Although chemoimmunotherapy (CIT) has dramatically improved response rates in patients with CLL, some CIT regimens are not well tolerated by many patients >or=70 years of age. METHODS: Sixty-four previously untreated patients with CLL and serum creatinine <1.5 times the upper limit of normal who met National Cancer Institute (NCI) 96-WG criteria for treatment received pentostatin (2 mg/m(2)), cyclophosphamide (600 mg/m(2)), and rituximab (375 mg/m(2)). The authors measured performance status at study entry and used age, weight, and baseline creatinine to calculate creatinine clearance (CrCl). RESULTS: Eighteen of 64 (28%) patients were ages >or=70 years. Although individuals ages >or=70 years were more likely to have delayed treatment cycles (28% vs 7%; P=.03), there were no significant differences in the number of cycles administered, need for dose reductions, or grade 3-4 hematologic, infectious, or other toxicities. No significant differences in overall response rate, complete response rate, or progression-free survival were observed by age. Twenty-five (39%) patients had a CrCl < 70 mL/min (range, 34-67). Although individuals with CrCl < 70 were more likely to require dose reduction (24% vs 5%; P=.05), there were no significant differences in the number of cycles administered or grade 3-4 hematologic, infectious, or other toxicities. No significant difference in overall response rate, complete response rate, or progression-free survival were observed between patients with CrCl >or= 70 mL/min and those with CrCl < 70 mL/min. CONCLUSIONS: In this clinical trial, the PCR regimen was well tolerated by older patients and individuals with CrCl 相似文献   

Combination chemotherapy with vinblastine, bleomycin and methotrexate in DTIC-resistant metastatic melanoma.

Fifteen patients with metastatic DTIC-resistant malignant melanoma were treated with vinblastine, bleomycin and methotrexate combination chemotherapy. Three patients showed an objective response (one complete response). The therapy was well tolerated and easy to administer. This combination appears to produce in DTIC-resistance patients a response rate similar to that obtained with DTIC.     

Factors affecting the outcome of patients with advanced urothelial cancer following chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin

Attempts were made to identify factors related to the response of patients treated with intravenous methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC). The subjects consisted of 54 patients with advanced urothelial cancer whose histological type was transitional-cell carcinoma. The effects of various factors on the response were studied using univariate analysis and a multiple logistic regression model. The following factors were included in the anlayses: (1) age, (2) sex, (3) performance status (PS), (4) primary site, (5) histological grade, (6) T category, (7) N category, (8) M category, (9) tumor status, and (10) dose of drugs. In all, 9 patients achieved a complete response and 23 showed a partial response, for an overall response rate of 59% (95% confidence limits, 46%–72%). Univariate analysis revealed that the PS, M category, and dose of drugs were related to the response, and there was a significant correlation among these three factors. In the multiple logistic regression model, the absolute value oft was high for the M category. The presence of distant metastases is an important factor in predicting poor efficacy for the present regimen. The management of metastatic disease will be the subject of further study in the treatment of advanced urothelial cancer.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Adriamycin, CCNU, and 5-fluorouracil in patients with advanced gastrointestinal cancer

Forty-one patients with measurable advanced gastrointestinal malignancy were treated with a combination of Adriamycin (doxorubicin), 5-FU (5-fluorouracil), and CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea). The response to therapy was evaluated every eight weeks. In addition to standard clinical examinations and laboratory tests to evaluate toxicity, 31 patients were asked to rank both the expected and experienced negative effects of the treatment. Although both patients with hepatocellular cancer and the patient with a soft tissue sarcoma responded to the regimen, only 1 of 38 patients with adenocarcinoma had a favourable response. The clinically measurable toxicity, principally to the gastrointestinal tract and bone marrow, was relatively mild. However, the patients' subjective evaluation of their treatment made the side effects appear more significant. The results suggest that this regimen deserves further evaluation in patients with hepatocellular cancer and soft tissue sarcomas.     

Bortezomib in combination with rituximab, dexamethasone, ifosfamide, cisplatin and etoposide chemoimmunotherapy in patients with relapsed and primary refractory diffuse large B-cell lymphoma

Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER). Fifteen patients were enrolled, of whom seven were refractory to first-line chemotherapy and only three had maintained first response for 1 year. Nine (60%) patients achieved objective responses, of which three (20%) were IWC-PET (International Workshop Criteria positron emission tomography) complete responses. Median progression-free survival was 3 months, and median overall survival was 10 months. At a median follow-up of 26 months, five patients (33%) remained alive. Treatment was well tolerated with no unexpected toxicity. Although response rates did not meet predefined criteria, activity was at least comparable to other second-line approaches despite a poor-prognosis patient population.     

Adriamycin, cyclophosphamide, ftorafur and tamoxifen (ACFT) in patients with advanced breast cancer

One hundred and six patients with advanced breast cancer were treated with chemoendocrine therapy consisting of adriamycin (40 mg/m2) i.v. on day 1 and cyclophosphamide (130 mg/m2) i.v. daily for 5 days every 3 weeks, ftorafur (500 mg/m2) and tamoxifen (40 mg) orally daily. Of 82 evaluable patients, 16 showed complete response (20%), 32 partial response (39%), 32 no change (39%), and two progressive disease (2%). The overall response rate was 59%, and the median duration of response was 16.3 (3.5-67+) months with a median survival time from the start of chemoendocrine therapy of 25.5 (3.5-67+) months. The median survival time of responders (32.5 months) was significantly longer than that of non-responders (15.3 months). The major toxicities were hair loss, G1 symptoms, and hematological toxicity, but these were clinically well tolerated. No serious cardiac, renal or liver damage was seen. These results indicated that the addition of tamoxifen to the ACF regimen increased the number of complete responses and prolonged the survival time of responders.