摘要:

Etoposide is a highly schedule-dependent agent. We previously reported that a 21-day schedule of oral etoposide had good activity in small cell lung cancer (SCLC). The current phase II study was designed to test the combination of 21-day oral etoposide with cisplatin in hopes of capitalizing on etoposide’s schedule dependency. Sixteen extensive stage SCLC patients were treated with cisplatin 100 mg/m2 day 1 plus 21 days of low-dose oral etoposide 50 mg/m2/ day. Chemotherapy was repeated every 28 days for 4 cycles. Blood counts were monitored weekly, and etoposide was discontinued if the leukocyte or platelet count dropped below 2.0 x 109/1 or 75 x 109/1, respectively. Fifteen of 16 patients were evaluable for response; 13 achieved either a complete (13%) or partial response (73%), for an overall response rate of 86% (95% confidence interval, 62-93%). Median response duration was approximately 7 months; median survival was not reached. Thirteen patients (81 %) received all the planned cycles of chemotherapy. In cycle 1 of chemotherapy, the median leukocyte nadir was2.8 x 109/1 (range, 0.1-6.3 x 109/1; median platelet nadir was 180 x 109/1 (range, 51-397 x 109/1). Life-threatening leukopenia ( < 1.0 x 109/l) was unusual (2 of 58 cycles). There was 1 treatment-related death. One patient developed mild renal insufficiency that resolved after therapy. Nonhematologic toxicities were uncommon, but alopecia occurred in all patients. These data do not suggest that a major survival benefit will be derived for patients with extensive stage SCLC by increasing the duration of etoposide administration when used in combination with cisplatin. A randomized study is needed to determine if this long-term schedule of etoposide plus cisplatin is superior to the standard schedule of etoposide plus cisplati

ISSN:0030-2414    

DOI:10.1159/000227108

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Thirty-eight patients with advanced colorectal adenocarcinoma were entered on a phase II trial of 5-fluorouracil (5-FU) in continuous infusion, using a portable pump. Half of the patients had been pretreated (n = 19) and 16 of them had received intravenous bolus 5-FU alone or in combination. At the first cycle patients received continuous intravenous 5-FU at the dose of 650 mg/m2 per day for 7 consecutive days. Doses were escalated during the following cycles and adjusted according to the toxicities encountered in the previous cycle. Treatment was repeated every 3 weeks. A mean dose of 750 mg/m2/day (500-1,000) was administered for a mean number of 10 (1-25) cycles. We observed 1 complete response, 7 partial responses for a response rate of 21 ± 13% (CI 95%), 16 had stable disease (42%) and 14 a progression (37%). In 2 patients subsequently the residual tumors could be excised after chemotherapy. Median survival was 13.5 months. Toxicity was: grade 2 leukopenia in 1 patient (3%), mucositis grade 2-4 in 11 patients (29%), diarrhea grade 2-3 in 7 patients (18%), and hand and foot syndrome in 12 patients (31%). There was a correlation between the mean dose administered and the responses. However no clear correlation was found between toxicity and tumoral response for the first two cycles. These results confirm the limited efficacy of continuous intravenous 5-FU and its good tolerance in ambulatory patients

ISSN:0030-2414    

DOI:10.1159/000227007

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Expression of c-myc protein was studied immunohistochemically in colorectal cancers using a monoclonal antibody, MYC-1. Immunoblotting assays with cellular lysates demonstrated a band of the gene products at the level of 60 kDa. c-myc-protein-positive tumor cells were observed in 43 (43.4%) of 99 specimens of colorectal cancers. There was no significant correlation between the incidence of MYC-1-positive tumors and clinicopathological findings. The rate of M YC-1 proteins occurring in patients with liver metastasis was significantly higher than that in patients without the metastasis. The rate of occurrence of DNA polymerase-a-positive cells in MYC-1 protein-positive tumors was significantly higher than in MYC-1 negative ones. The results suggested that MYC-1 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.

ISSN:0030-2414    

DOI:10.1159/000227008

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Non-small cell lung cancer (NSCLC) is a major health problem in the United States and in many other parts of the world. Identification of systemic therapy that can maintain or improve quality of life and prolong survival is essential because locally advanced disease or distant metastasis is found in the majority of these patients. A variety of combination regimens have produced response rates of 20% or greater in stage IV NSCLC patients in coopertive group trials, including studies conducted within the Eastern Cooperative Oncology Group (ECOG). Although no regimen has emerged as clearly superior, the highest 1-year survival rate (25%) in ECOG trials was observed in EP(etoposide/ cisplatin)-treated patients. Subsequently, a randomized trial in which EP was compared to etoposide/carboplatin revealed no significant differences in survival or response rate, and toxicity was slightly less with etoposide/carboplatin. Results from recent phase II trials in which stage III NSCLC patients received preoperative EP and concurrent thoracic irradiation have shown response rates of 65-85%, as well as acceptable toxicity and surgical morbidity and mortality. Future stage IV NSCLC trials should include studies of platinum/ etoposide plus new agents. Also a study comparing platinum/etoposide versus supportive care should be considered. The objectives of this study would be to compare survival, quality of life, and cost-effectiveness ratio. The results of recent phase II studies in stage III NSCLC patients suggest that preoperative cisplatin/etoposide and concurrent thoracic irradiation should be considered for evaluation in a phase III trial in stage IlIa NSCLC patients and that this regimen should also be evaluated in stage Illb patients.

ISSN:0030-2414    

DOI:10.1159/000227110

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effects of chemotherapy on the growth of colony forming unit-granulocyte macrophage (CFU-GM) from the bone marrow (BM) and peripheral blood (PB) of 8 patients with lung cancer were studied by using recombinant interleukin-3, granulocyte macrophage-colony stimulating factor, and granulocyte-colony stimulating factor. After chemotherapy, the kinetics of CFU-GM depend on the type of chemotherapeutic regimens used: a rebound overshoot of CFU-GM in the PB was seen in the 4 patients treated with cisplatin plus etoposide (PVP) but not in the 4 patients treated with cisplatin plus mitomycin plus vindesine (CMV). In the BM, the recovery of CFU-GM was more retarded in patients treated with CMV relative to that seen in patients treated with PVP. The results obtained in simultaneous cultures revealed the differences between CMV and PVP in the kinetics of chemotherapy-induced myelosuppression. Determination of the optimal timing of in vivo use of hematopoietic growth factors after cytoreductive chemotherapy requires careful experimental design.

ISSN:0030-2414    

DOI:10.1159/000227009

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Once-a-day ceftriaxone and amikacin was administered in case of fever to 46 neutropenic patients attending day hospital for hematologic malignancies. All patients were admitted to a short-term ward for infective complications, but were discharged in the event of prompt disappearance of fever and of clinical signs of infection continuing their therapy either by daily reporting to the hospital, or at home. Response to the initial empiric therapy was obtained in 37 cases (76%). Twenty-four patients who promptly responded to therapy completed their treatment on an outpatient basis, their mean number of days of hospitalization being reduced to 4.6 versus a mean of 9.6 days in the overall patient population being considered. Since the outpatient treatment accounted for 21 % of the antibiotic therapy administered, the above treatment may result in cost containment and better quality of life for patients, provided that these data are confirmed by prospective randomized studies.

ISSN:0030-2414    

DOI:10.1159/000227010

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Based on in vitro experiments suggesting cytotoxic activity of at least a supra-additive effect, a phase I clinical study of carboplatin/cisplatin sequential combination treatment was carried out in 17 patients with non-small cell lung cancer (NSCLC). At 300 mg/m2 carboplatin and 80 mg/m2 cisplatin, the median leukocyte nadir was 2.6 x 109/l half the patients exhibited grade 3 or higher leukopenia. When cisplatin was increased to 100 mg/m2 the leukocyte nadir fell to 0.7 x 109/l and grade 3 or 4 leukopenia was universal. A phase II pilot study of carboplatin 300 mg/m2 followed by 80 mg/m2 cisplatin was subsequently initiated in patients with NSCLC. Currently, 11 patients have entered the study and 8 have been added from the phase I study. Interim analysis shows that 8 patients have had at least a partial response to cisplatin/carboplatin, for a response rate of 42%. The response rate in previously untreated patients was 47%. At this time, 12 patients are alive but median survival has not yet been reached. No particularly serious adverse effects were observed. Four to five repeat administrations are planned in responders. Future studies with the cisplatin/carboplatin combination in NSCLC are warranted.

ISSN:0030-2414    

DOI:10.1159/000227111

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Interferons are known to modulate several cellular functions by the induction of different proteins. In our study interferon-gamma and -alpha augmented presentation of one specific ovarian cancer antigen recognized by the antibody OV632 on the cell surface on one of four ovarian carcinoma cell lines in vitro (HTB-77). The interferon-gamma effect reached a maximum after 24 h of treatment. Both HLA-DR and OV632 antigen expression were increased by interferon-gamma on HTB-77 cells whereas the two cell lines OVCAR-3 and 2780, which respond to an interferon-gamma treatment with a reduced proliferation and induction of HLA-DR, and also the interferon-resistant CRL-1572 were found to be resistant regarding OV632 epitope modulation. The demonstration of OV632 expression provides an important insight into the potential regulatory mechanism governing this tumor marker.

ISSN:0030-2414    

DOI:10.1159/000227011

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Forty-two patients with unresectable non-small cell lung cancer (NSCLC) were treated with carboplatin (300, 350 or 400 mg/nr) and 21 days of oral etoposide (50 mg/m2/day). Thirty-three patients were evaluable for response (too early to assess the remaining patients) and 9 patients (27%) achieved a partial remission. Median survival was 29 weeks (range, 4+ to 71 + weeks). The primary toxicity was myelosuppression. Leukocyte and platelet count nadirs occurred between days 22 and 29. In cycle 1, median leukocyte nadir was 2.8 x 109/1 and the platelet nadir was 142 x 109/1- Nonhematologic toxicities were modest and included alopecia in all patients, mild nausea, mild to moderate diarrhea, and an occasional increase in serum creatinine. Carboplatin plus oral etoposide is a tolerable outpatient regimen with modest activity against unresectable NSCLC.

ISSN:0030-2414    

DOI:10.1159/000227112

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This study examined the influence of the oxygen-derived free radical removing agents allopurinol and dimethyl sulphoxide (DM SO) on the occurrence of hepatic metastases and on the survival rate in the rat with 1,2-dimethylhy-drazine (DMH)-induced colonic tumours. At 10 weeks of age, rats were sub-cutaneously injected every week with 10 mg per kg body weight of DMH for 28 weeks. This produced colonic carcinoma in 80% of animals. The rats that were at this stage continued on their drinking water developed multiple hepatic metastases within 3 months and died at the age of 14.9 ± 0.3 months (mean ± SEM). Administration of 1,2 or 5% allopurinol or DMSO for drinking after production of the colonic tumours prevented the development of hepatic metastases 3 months later and significantly (p < 0.01) extended survival to at least 22.1 ± 0.1 months of age (mean ± SEM). The results suggest that in the rat with colonic carcinoma, removing oxyradicals impairs the development of hepatic metastases and prolongs survi

ISSN:0030-2414    

DOI:10.1159/000227012

出版商:S. Karger AG    

年代:1992

数据来源: Karger