Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible synergism of cisplatin (P) and 5-fluorouracil was studied in 38 consecutive patients with advanced or metastatic colorectal carcinoma. Cisplatin 60 mg/m2 i.v.q. 4 weeks and fluorouracil 600 mg/m2 i.v. weekly were administered for at least 2 cycles, on an out-patient basis, to 24 males and 14 females with a median age of 57 years and a median PS of 80 (Karnofsky). Evaluable lesions were: primary unresectable tumor in 2 patients, local recurrence in 11, liver, lung, bone and soft tissue metastases in 21, 7, 2 and 3 patients respectively. With a median number of 3 cycles administered to 35 evaluable patients, 6 partial responses, 16 unchanged and 13 progressions were observed. Responses were observed in the liver (2 patients), lungs (1) and soft tissues (3). Median remission duration was 15 weeks, median duration of 'unchanged' was 12 weeks. The overall median survival was 24 weeks (30.5 weeks for responders and 22.5 weeks for non-responders). Six patients were pretreated with chemotherapy not containing cisplatin (mainly adjuvant 5-FU). None of them responded. Toxicity was very tolerable with moderate nausea, vomiting and alopecia in the majority of the patients; bone marrow toxicity was generally mild with no blood transfusions required, no complications of myelosuppression (sepsis or bleeding) and no chemotherapy-related deaths. In this experience the combination of low dose cisplatin with fluorouracil, does not appear to significantly enhance 5-FU toxicity and the response rate is not superior to that reported with 5-FU alone. However, better designed schedule combinations with optimal doses, sequences and exposure time of the 2-drug regimen, seem necessary to obtain the biochemical events that support the potentiation.
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PMID:Cisplatin and 5-fluorouracil combination chemotherapy in advanced and/or metastatic colorectal carcinoma: a phase II study. 365 87

Sixteen patients with advanced evaluable urothelial cancer were treated with a chemotherapy regimen of cyclophosphamide, adriamycin and cisplatin (CAP). Cisplatin 50 mg/m2 and adriamycin 30 mg/m2 were given on the first day and cyclophosphamide 200 mg/m2 was given from the second to the fifth day. This course was repeated every 3 weeks. The objective response rate was 25% (4 of 16 patients), with 1 patient achieving complete remission. The survival time of responders was longer than that of nonresponders, although the difference was not significant (generalized Wilcoxon method). As side effects, nausea with vomiting (43.8%), renal dysfunction (6.3%), anemia (12.5%), leucopenia (12.5%), thrombocytopenia (25.0%), alopecia (68.8%), heart failure (6.3%) and peripheral neuropathy (6.3%) were noticed. One patient died of sepsis due to agranulocytosis and another died suddenly of heart failure.
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PMID:[Combination chemotherapy of cyclophosphamide, adriamycin and cisplatin in advanced urothelial cancer]. 367 92

The efficacy of two chemotherapy regimens for recurrent and inoperable squamous cell carcinoma of the head and neck is reported. All patients had failed prior surgery and/or radiotherapy. 23 patients (group A) were treated with Cisplatin 120 mg/m2 and Adriamycin 60 mg/m2. 21/23 were evaluable for tumour response. The overall response rate (RR) was 28.5% (6/21, 2 CR and 4 PR). Methotrexate 250 mg/m2 with Leucovorin-Rescue 5 X 10 mg/m2 and 5-Fluorouracil 600 mg/m2 were administered to 28 patients. In 26 evaluable patients a RR of 38.4% (10/26, 5 CR and 5 PR) was achieved. The responders in groups A and B had a median survival of 98 and 85.5 weeks respectively and the non-responders 27 weeks in both groups. Nausea, vomiting and alopecia were common and severe in the DDP/ADM group. The major toxic effect of MTX/5-FU was neutropenia with two associated deaths from septicemia, although subjective side-effects were almost completely absent. MTX/5-FU can be recommended for the palliative treatment of recurrent squamous head and neck cancer because of an acceptable response rate, good subjective tolerance and the possibility of outpatient treatment.
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PMID:[Chemotherapy of recurrent squamous cell carcinomas in the ENT area with cisplatin/adriamycin (DDP/ADM) and methotrexate/5-fluorouracil (MTX/5-Flu): a retrospective comparison of 2 protocols]. 374 8

Cisplatin plus 5-FU appears to have significant additive activity in various tumors, such as head and neck carcinoma and esophageal cancer. A partial explanation for this may be drug synergism, which has been noted in the L1210 leukemia model. Based on these data, a prospective trial of weekly bolus 5-FU (15 mg/kg) and cisplatin (60 mg/m2) given every 3 weeks was initiated at Indiana University. Forty-one patients, of whom 38 are fully evaluable for response, were treated with these two drugs. Ten partial and one complete response (complete + partial response rate = 29%) were observed in the 38 evaluable patients. Thirteen additional patients had stable disease for greater than or equal to 3 months. The median durations of remission and survival time were 6 and 10.3 months, respectively. Myelosuppression was unusually severe, with granulocyte counts less than 1000/mm3 in 65% of patients, including four patients with granulocyte count nadirs less than 100/mm3. Three patients developed granulocytopenic fever, with two drug-related deaths (sepsis, hyperosmolar coma). Nearly all patients had nausea and vomiting, but this was not a treatment-limiting toxic effect in any patient. Although this combination suggests a higher response rate than usually seen with bolus iv 5-FU in colon cancer, a trial comparing 5-FU alone or with cisplatin to determine whether true synergy exists is currently underway.
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PMID:Cisplatin plus 5-FU for the treatment of adenocarcinoma of the colon. 407 11

Cisplatin and etoposide combination was used in 94 patients with measurable or evaluable bronchogenic squamous cell carcinoma or adenocarcinoma. The overall response rate was 38% with four complete remission (CR). In patients with locoregional disease who did not receive any prior anticancer therapy the response rate was 56% (19/34) with three CR, significantly (P = 0.02) higher than that observed in the other patients (28%). The overall median duration of response was 36.7 weeks. Patients with locoregional disease who did not receive any prior anticancer therapy had a median duration of response of 43.6 weeks; longer than that (27.5 weeks) in the other patients. Overall, responding patients survived significantly longer (P less than 0.0001) than non responders (median survival 60.0 weeks versus 23.0). Toxicity was tolerable; gastrointestinal side effects were occasionally responsible for discontinuation of therapy and sepsis was the cause of death in two neutropenic patients. No serious nephrotoxicity was observed. The combination of cisplatin and etoposide should probably be tested in combination with surgery of radiotherapy.
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PMID:Combination chemotherapy with cisplatin and etoposide in bronchogenic squamous cell carcinoma and adenocarcinoma. A study by the EORTC lung cancer working party (Belgium). 689 Apr 4

Cisplatin (P) and 5-fluorouracil (5FU) have demonstrated activity for the treatment of squamous cell carcinoma of the esophagus. Previous studies have shown that leucovorin (L) may potentiate the antitumoral activity of 5FU, so we tested the combination P-5FU-L in 31 patients with inoperable squamous cell esophageal carcinoma. Chemotherapy consisted of P 20 mg/m2 in 4 h, followed by L 200 mg/m2 in 2 h and 5FU 600 mg/m2 in 18 h. This schedule was repeated for 5 days every 4 weeks. The treatment plan included three courses of chemotherapy followed by radiotherapy. The overall response rate was 58% (95% CI = 39-76%), with one complete remission (3%), and 61% of patients reported an improvement in dysphagia. Gastrointestinal toxicity was the main side effect: grade 3-4 mucositis appeared in 19% of patients, grade 3-4 nausea/vomiting in 13%, and grade 3-4 diarrhea in 6.5%. There was one toxic death caused by neutropenia and sepsis. Nineteen patients received local radiotherapy after chemotherapy, which increased the overall response rate to 63% (5% complete responses). Dysphagia improved in 75% of them. The median survival for all patients was 11 months. This study shows that sequential therapy with P-5FU-L and radiotherapy achieves a high response rate as well as adequate symptomatic relief in patients with inoperable esophageal cancer. The results justify further evaluation of P-5FU-L in patients with earlier-stage disease.
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PMID:Phase II study of cisplatin, 5-fluorouracil, and leucovorin in inoperable squamous cell carcinoma of the esophagus. ONCOPAZ Cooperative Group, Spain. 893 75

A phase I study was performed to establish the optimum dose for combination therapy with infusional cisplatin and irinotecan (CPT-11) in non-small-cell lung cancer (NSCLC). The subjects were 20 patients with a performance score of 0-2 with untreated advanced NSCLC. Cisplatin was administered by 5-day continuous intravenous infusion at 20-25 mg/m2 per day. CPT-11 was administered by bolus infusion at a starting dose of 20 mg/m2 on days 1 and 8 or 60 mg/m2 per day on day 1 alone, followed by serial increments of 20 mg/m2. Since grade 4 granulocytopenia was observed in two of the five patients receiving 20 mg/m2 per day cisplatin (days 1-5) and 100 mg/m2 CPT-11 (day 1), and since one of them developed severe pneumonia and sepsis associated with the granulocytopenia, the regimen was considered to be intolerable. In the same patient, grade 4 thrombocytopenia and grade 3 diarrhea were observed. Therefore, the optimum dose appeared to be 20 mg/m2 per day (days 1-5) for cisplatin and 80 mg/m2 (day 1) for CPT-11. The side effects were grade 2 diarrhea in one of three patients, and grade 2 vomiting in three patients, but grade > or = 2 hemotoxicity was not observed. This combined regimen resulted in a partial response in 9 out of 19 assessable patients. The dose-limiting factor in this combination therapy was granulocytopenia, and a high efficacy rate was obtained.
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PMID:A phase I study of irinotecan and infusional cisplatin for advanced non-small-cell lung cancer. 902 73

Cisplatin and carboplatin are platinum-based chemotherapeutic agents with broad antitumor activity and significantly different toxicity profiles. They are commonly used in combination with etoposide (VP-16) in chemotherapeutic regimens. We conducted a phase I trial using the combination of cisplatin, carboplatin, and etoposide in advanced malignancy, aimed at delivering a higher dose intensity of active platinum species while taking advantage of their nonoverlapping toxicities. Etoposide was added because of its synergistic action with platinum compounds. The initial chemotherapy regimen consisted of carboplatin 180 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 60 mg/m2 on days 1-3. Dose was escalated based on toxicity observed at each level and separately for patients with a previous history of chemotherapy and for those with no prior treatment. Thirty-six patients were entered in the study, and 33 were evaluable. Hematologic toxicity was dose limiting. Grade 3-4 leukopenia was noted in 22 of 33 (66%) patients and grade 3-4 thrombocytopenia was noted in 16 of 33 (48%). No serious bleeding complications occurred. There was one treatment-related death due to neutropenic sepsis. Nonhematologic toxicity was mild and not dose limiting. Ototoxicity and nephrotoxicity were minimal. No complete responses (CR) occurred. Nine of 33 (27%) patients had objective responses, including 3 patients with adenocarcinoma of the esophagus or gastroesophageal junction who had failed prior chemotherapy. Fifteen of 33 (45%) patients had stable disease. The maximum tolerated dose varied for patients who had received prior chemotherapy and for those who were previously untreated. For further studies, the recommended dosing for previously untreated patients is carboplatin 300 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 105 mg/m2 on days 1-3. The recommended dosing for patients with a history of prior chemotherapy is carboplatin 220 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 75 mg/m2 on days 1-3. The combination of cisplatin, carboplatin, and etoposide merits further testing in phase II trials.
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PMID:Combination chemotherapy with cisplatin, carboplatin, and etoposide in advanced malignancy: a phase I trial. 934 36

Gastric cancer is the most chemosensitive adenocarcinoma among digestive neoplasms. A few years ago, we performed a phase II trial with the FLEP regimen, in which fluorouracil (5-FU) and leucovorin are combined with etoposide and cisplatin (Platinol). This regimen resulted in a 39% response rate and high toxicity. Then we used the combination UFT (tegafur and uracil)/leucovorin/etoposide: UFT 390 mg/m2/day orally on days 1 to 14; leucovorin 500 mg/m2 i.v. day 1, and 15 mg/12 h orally on days 2 to 14; and etoposide 100 mg/m2 i.v. on day 1 and then 200 mg/m2/day orally on days 2 and 3. Forty-six patients received a median of five courses. Five patients (11%) achieved a complete response and 12 (26%) a partial response, for an overall response rate of 37%. The response rate was 50% in patients with an Eastern Cooperative Oncology Group performance status of 0 to 1. Grades 3 to 4 toxicities appeared as follow: 17% of patients had diarrhea, 11% had nausea/vomiting, and 13% of patients had anemia. One patient died of neutropenia and sepsis. The median survival time was 9 months. In summary, UFT/leucovorin/etoposide is effective and moderately toxic in patients with advanced gastric cancer. A new trial with UFT/leucovorin/epirubicin is ongoing.
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PMID:The UFT/leucovorin/etoposide regimen for the treatment of advanced gastric cancer. Oncopaz Cooperative Group. 934 81

Cisplatin-based combination chemotherapy is frequently used to treat patients with carcinoma of unknown primary site (CUPS). Response rates in the literature range from 12% to 26% and median survival from 5 to 7 months. The goal of this study was to evaluate the combination of carboplatin and prolonged oral etoposide in patients with CUPS, with the hope of minimizing toxicity but improving efficacy and convenience. Treatment consisted of carboplatin, 300 mg m(-2) on day 1, and oral etoposide 50 mg on days 1-20, every 4 weeks for up to nine cycles. A total of 33 patients were treated and all were evaluable for toxicity. Non-haematological toxicity was mild to moderate, with the exception of one case of grade 4 stomatitis. Grade 4 leucopenia was observed in eight (24%) patients and sepsis in four (12%), with two and possibly three treatment-related deaths. For the 26 patients evaluable for response, the response rate was 23% with responses lasting a median of 11 months (range 7-13 months), with one patient still responding at 12 months. An additional nine patients (35%) had stable disease. Median survival for all patients was 5.6 months (range 2 weeks to 33 months). The combination of carboplatin with prolonged oral etoposide has moderate activity similar to that of other platinum-based regimens and is a well tolerated, convenient, outpatient regimen. Dosing according to estimated creatinine clearance to achieve a carboplatin AUC of 6.0 mg ml(-1) min might have decreased the incidence of severe myelotoxicity without compromising the regimen's efficacy.
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PMID:A multicentre phase II study of carboplatin and prolonged oral etoposide in the treatment of cancer of unknown primary site (CUPS). 964 62


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