Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suggestions of a dose-response effect for cisplatin in non-small-cell lung cancer have contributed to the development of very high-dose cisplatin regimens (200 mg/m2 per cycle). We treated 53 eligible patients with metastatic or recurrent non-small-cell lung cancer with a combination of 100 mg/m2 cisplatin and 4 mg/m2 vinblastine, each given on days 1 and 8 of a 28-day cycle. We observed no complete response and 4 partial responses (8%). Median survival was 6 months. Toxicities of grade III or greater included leukopenia (11 cases), nausea/vomiting (6 cases), thrombocytopenia (2 cases), anemia (2 cases), and elevation of transaminase (1 case). Neurotoxicity has been reported to be a major problem in several other very high-dose cisplatin regimens. The low level of neurotoxicity observed in this study may be attributable to the median cumulative cisplatin dose of less than 600 mg/m2. This vinblastine/very high-dose cisplatin regimen showed minor activity against non-small-cell lung cancer. The level of activity did not surpass that of standard-dose (100 mg/m2 per cycle) cisplatin-containing regimens.
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PMID:Treatment of non-small-cell lung cancer with vinblastine and very high-dose cisplatin. A Southwest Oncology Group study. 164 6

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.
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PMID:Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer. 165 2

The combination of dichloromethotrexate, cisplatin, and infusional 5-fluorouracil was evaluated as treatment for non-small-cell lung cancer in a phase II trial using 43 evaluable patients. Grade III or IV toxicity included thrombocytopenia (21%), leukopenia (14%), nausea/vomiting (14%), mucositis (9%), infection (5%), and other (16%). There were six responders (14%), with a 95% confidence interval of [5%, 28%]. Two additional patients achieved a 50% reduction in cross-sectional tumor size that was not documented twice. Median survival time was 6.5 months. This combination is not considered sufficiently active for further evaluation in this disease.
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PMID:Dichloromethotrexate, infusional cisplatin, and infusional 5-fluorouracil for locally advanced or metastatic non-small cell lung cancer. A MAOP study. 165 78

In a multicentre phase II trial, 20 patients with advanced pancreatic carcinoma were treated with 5-fluorouracil, 4-epidoxorubicin and mitomycin C, in which 4-epidoxorubicin was administered by escalated dose and split course (FEM II). From among 12 patients evaluable for response, 2 partial and 1 minimal remission were observed, suggesting a response rate of 25%. Four patients (30%) showed a no change and 5 progression. The median survival of all patients was 3.4 months, of the responders 8.4 months, of those with no change 5.2, and of those showing progression 3.4 months. Considerable nausea/vomiting and leukopenia was observed. The preliminary data suggest that the FEM II regimen does not offer any progress in terms of efficacy, survival and toxicity for advanced pancreatic carcinoma.
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PMID:[Treatment of advanced pancreatic cancer with 5-fluorouracil, 4-epidoxorubicin and mitomycin C (FEM II). From the Chemotherapy of Gastrointestinal Tumors Group]. 169

A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using pirarubicin (4'-0-tetrahydropyranyladriamycin, THP) was performed. Although adriamycin has been widely utilized for chemoembolization on the hepatocellular carcinoma, myocardial toxicity has been occasionally observed as its serious side effect. THP has an advantage that myocardial and gastrointestinal complications are less frequent than adriamycin. Ten patients with hepatocellular carcinoma were included in this study. Emulsion of 30-60 mg of THP and lipiodol was administered through a catheter inserted into the right or left hepatic artery, and thereafter, transarterial embolization was performed. PR was observed in seven of the ten patients and MR in two. Only one patient showed NC. Serum alpha-fetoprotein levels decreased in nine of the ten patients, and PIVKA II in the peripheral blood disappeared in all five patients that had been positive before the chemo-embolization four weeks after the treatment. Side effects included nausea in two patients just after administration of THP, but leukopenia below 2,000/cmm, was not observed in any of the patients. No other serious side effect was observed. From these results, THP was suggested to be a useful chemotherapeutic agent for hepatocellular carcinoma.
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PMID:[A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using 4'-0-tetrahydropyranyladriamycin]. 169 81

Sixty-six patients with locally advanced (Stages III and IV) carcinoma of the head and neck were treated with three cycles of induction chemotherapy, consisting of cisplatin, fluorouracil (FU) infusion, bleomycin, mitomycin, and hydroxyurea, followed by radiotherapy and/or surgery. There were 48 men and 18 women with a median age of 55 years (range, 18 to 75 years) and Karnofsky performance status of 80 (range, 40 to 90). Primary site was nasopharynx (28 patients), followed by larynx (12) and others (26). Forty-one (62%) patients were presented with Stage IV disease. The response rate to induction chemotherapy was 27% complete response, 50% partial response, 20% stable disease, and 3% progressive disease. There was no significant difference in response rate between patients with cancer of nasopharynx or other sites (P greater than 0.1). Survival was 61% at 24 months. Patients with cancer of nasopharynx had a better survival than those with other primaries (P = 0.033). Toxicities from chemotherapy included alopecia (73%), nausea/vomiting (66%), leukopenia (54%), stomatitis (36%), anemia (32%), thrombocytopenia (16%), and diarrhea (9%). Grade IV toxicity was not observed. Induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and FU alone. It can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck. Chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers.
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PMID:Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region. 169 26

Twenty-five adult patients with resistant or early relapsing Hodgkin's disease have been treated with CAV combination chemotherapy (CCNU, melphalan and etoposide). All patients had previously received both MOPP and ABVD regimens (23 patients as primary therapy and two as first salvage). High-energy radiotherapy had been administered in one case. The CAV chemotherapy was used as first salvage therapy in 15 cases (60%); the remaining patients had been heavily pretreated with different regimens including alkylating agents, vinblastine, and/or nitrosourea derivatives before CAV for multiple relapses or progressive disease. At the initiation of CAV chemotherapy, 64% of patients had extranodal disease (20% with more than one site), and bone marrow was involved in 16% of total cases. Thirty-two percent of CAV patients had progressed during primary therapy, while only 20% of cases had relapsed after complete remission (CR). The CR rate after CAV therapy was 17% (4 of 24); partial responses were observed in 33% of patients, giving an overall response rate of 50%. The response was influenced by the presence of nodal disease and by a prior response to chemotherapy. Considering the 15 patients who received CAV therapy as first salvage, the CR rate was 37%. The median survival from the initiation of CAV therapy was 23 months for the whole group of patients, and was not reached at 2 years for those who received CAV as first salvage therapy. Toxicity consisted of nausea (100% of cases), vomiting (63%), reversible alopecia (83%), mild to moderate leukopenia and thrombocytopenia (54% and 21%, respectively). No therapy-related deaths were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CAV chemotherapy (CCNU, melphalan, etoposide) as salvage treatment for relapsing or resistant Hodgkin's disease. 170 10

A phase I trial of fazarabine (ara-AC, 1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 24 adults with solid tumor malignancies. The majority of patients had received prior marrow-suppressive therapy. Level 7 (54.5 mg/m2/h for 24 h) was the maximum tolerated dose since during 6 evaluable first courses, 2 episodes of grade 4 granulocytopenia and 3 episodes of grade 3 occurred. Moderate thrombocytopenia also occurred at level 7 with 3 episodes of grade 1 and 1 episode of grade 4 thrombocytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir WBC through 47 courses had a linear relationship with plasma steady-state concentrations of ara-AC. The only other toxicity noted was moderate nausea/vomiting, which did not appear to be dose related. Plasma steady-state concentrations of ara-AC were reached in all patients within 4-6 h and ranged from 1.1 microM (11 mg/m2/h for 24 h) to 7.5 microM (54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 1-7, was 592 +/- 147 (SD) ml/min/m2 which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatric and Medicine Branches, respectively. There were no objective disease responses during the trial. The recommended adult phase II dose for a 24-h infusion of ara-AC is 45-50 mg/m2/h.
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PMID:Phase I clinical trial of fazarabine as a twenty-four-hour continuous infusion. 170 65

A combination of mitomycin C, vindesine and melphalan was administered to 33 patients with heavily pretreated refractory breast cancer. The overall response rate was 27% with a mean duration of more than 10.2 months. A stabilization with a mean duration of 5.1 months was seen in 56% of cases, while 20% of patients progressed. Gastrointestinal toxicity, mostly grade 1 or 2 nausea/vomiting was seen in 85% of cases, grade 1 or 2 leukopenia in 60% of patients, and grade 1 or 2 thrombocytopenia in 42%. Considering the good compliance of this regimen and the poor prognosis of patients with refractory advanced breast cancer, this combination can be useful as a palliative treatment of breast carcinoma.
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PMID:Combination chemotherapy with mitomycin C, vindesine and melphalan for refractory metastatic breast cancer. 170 43

Preclinical and clinical studies demonstrate that the selective antitumor activity of fluorouracil (5-FU) is enhanced by agents which perturb certain intracellular nucleotide pools. We previously demonstrated that the combination of N-phosphonacetyl-L-aspartate (PALA), which depletes pyrimidine nucleotide pools, and 5-FU yielded a 43% response rate among 37 assessable patients with colorectal carcinoma. In preclinical tumor models, 6-methylmercaptopurine riboside (MMPR), an inhibitor of purine synthesis, elevates phosphoribosylpyrophosphate (PRPP) pools and promotes the anabolism of 5-FU to fluorinated nucleotides. In vivo, the addition of MMPR enhances the therapeutic efficacy of PALA-5-FU. In a phase I trial, we sought to determine the optimal dose and schedule of MMPR in combination with PALA (250 mg/m2 on day 1) and 5-FU (1300 mg/m2 by 24-hour infusion on day 2). MMPR (75-225 mg/m2) was given intravenously on day 1 to 27 patients with solid tumors (15 colorectal, seven breast, five other). Toxic effects were mild to moderate and included leukopenia, mucositis, nausea, or rash. Two of seven patients given MMPR at 225 mg/m2 had grade 3 diarrhea. PRPP was measured using a [14C]orotic acid 14CO2 release assay in tumor biopsy specimens obtained before and 12 hours and 24 hours after MMPR doses were given to 20 patients. The addition of MMPR elevated PRPP pools in human solid tumors. At 12 hours after treatment, two (50%) of four patients showed a twofold or greater elevation of PRPP at the MMPR dose level of 75 mg/m2; a similar elevation was observed in five (71%) of seven patients given 150 mg/m2 MMPR and in three (43%) of seven patients given 225 mg/m2 MMPR. At 24 hours after treatment, results for the respective dose levels of MMPR were two (33%) of six patients, one (20%) of five patients, and four (57%) of seven patients. Administration of the two highest MMPR dose levels appeared to result in a greater increase in tumor PRPP levels. However, toxicity was greater at the 225 mg/m2 dose level; therefore, the 150 mg/m2 dose level was favored. Tumor levels of PRPP decreased between 12 hours and 24 hours in nine (56%) of 16 patients. This time course indicates that MMPR should be administered at the beginning of the 24-hour infusion of 5-FU.
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PMID:Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine riboside: optimization of 6-methylmercaptopurine riboside dose and schedule through biochemical analysis of sequential tumor biopsy specimens. 171 7


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