Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days. 133 81

We treated 34 chemotherapy-naive patients with stage IIIb or IV non-small cell lung cancer with trimetrexate 150-200 mg/m2 intravenously over 30 minutes every two weeks. Six of 31 evaluable patients (19%) achieved a partial response. The major toxic effects from this regimen were myelosuppression, nausea/vomiting, and skin rash. We conclude that this well-tolerated schedule of trimetrexate has significant activity as a single agent against non-small cell lung cancer.
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PMID:Phase II trial of trimetrexate for unresectable or metastatic non-small cell bronchogenic carcinoma. 133 71

Cisplatin has many toxic effects; emesis, impairment of renal function, myelosuppression, peripheral neuropathy, ototoxicity and renal tubular wasting. We used MVP regimen (Mitomycin C, Vp-16, and Cisplatin) in advanced Non-Small Cell Lung Cancer (NSCLC). Using hydration and prophylactic supplementation of sodium and potassium before and during chemotherapy, we have observed the development of hyponatremia in 48 courses (43%), hypokalemia in 23 courses and hypomagnesemia in 11 courses. Some patients showed abnormalities of renal function in 16 courses. All the electrolyte depletion and renal problem was corrected before next courses by hydration and replacement of the wasting. Frequent measurement of serum cation and appropriate replacement are recommended when high dose Cisplatin containing regimen is used in chemotherapy of neoplasms.
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PMID:Renal salt wasting in patients treated with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small cell lung cancer. 133 77

The response rate and survival obtained with the combined regimen of bleomycin, ifosfamide, and cis-platinum (BIP) were analyzed in a series of 24 patients with recurrent cervical carcinoma in previously irradiated area. The doses were 30 mg, 5000 mg/m2, and 50 mg/m2, respectively. Mesna was given simultaneously (6000 mg/m2). None of the patients were treated with prior chemotherapy. All the patients were evaluable for toxicity and 20 for response. The median survival in patients evaluable for response was 9 months. No complete and 3 partial responses (15%) were observed, with a median duration of survival of 10+ months (range, 9(+) -16). Stable disease was observed in 8 patients (40%) with a median duration of survival of 9.5 months (range, 6(+) -20). Progressive disease was observed in 9 patients (45%) with a median duration of survival of 6 months (range, 3-25+). Four patients received one course only because of toxicity. One of these patients died at home 6 days after the first course, probably because of dehydration. The main toxicities were myelosuppression, renal impairment, alopecia, and nausea/vomiting. In conclusion, the BIP regimen has considerable toxicity. We were not able to confirm the high response rates earlier reported in pelvic recurrence inside a previously irradiated area. Emphasis in future studies must continue to be placed on the development of more active single agents and combinations.
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PMID:Bleomycin-ifosfamide-cis-platinum (BIP) in pelvic recurrence of previously irradiated cervical carcinoma: a second look. 137 61

Nineteen patients, nine men and 10 women, with advanced adenoid cystic carcinoma (ACC), were treated with cisplatin either alone or in combination with doxorubicin and bleomycin. Median age was 51 years (range: 32-73 years). Two groups of patients were distinguished: Group 1 (N = 10) received single-agent cisplatin (50-120 mg/m2 IV every 4 weeks) for locoregional recurrence (N = 4), pulmonary metastases (N = 5), or as neoadjuvant therapy (N = 1). Five patients failed previous chemotherapy. No objective responses were observed, five patients showed stabilization of their disease for a median duration of 20 months (range: 3-50 months). Group 2 (N = 9) received a combination of cisplatin (20 mg/m2 IV on days 1-5), doxorubicin (50 mg/m2 IV on day 1), and bleomycin (30 mg IV on days 1-5), every 3 weeks. A complete remission (CR) was seen in one patient, lasting for 2 years, a partial remission (PR) in two patients (duration: 6 months and 6 years) (33%), and a stable disease (SD) in five patients (median duration: 15 months; range 3-24 months). One patient showed progression from the start. The observed toxicity was acceptable: dose reduction was required in five patients for myelosuppression or impairment of renal function; vomiting grade III (WHO) was seen in 10 patients. The median progression-free survival was 36 months (range: 7-77 months). Median overall survival was 81 months (range: 14-216 months). The role of cisplatin in this disease remains questionable.
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PMID:Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and neck. 138 39

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
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PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

Between December 1982 and November 1990, 31 patients with advanced urothelial carcinoma were treated with one of two combination chemotherapy regimens. A total of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2 cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5-fluorouracil (5-FU) given intravenously every day for as long as possible (CF-Mito regimen). After the patient had been discharged from the hospital, the same treatment with CF-Mito was performed except that 180 mg/m2 5-FU was replaced by 400 mg/m2 UFT (a mixture of tegafur and uracil) given orally. A total of 11 patients whose tumor had relapsed during the first-line treatment were given 60 mg/m2 cisplatin, 40 mg/m2 Adriamycin, and 40 mg/m2 methotrexate intravenously every 28 days (PAM regimen). In all, 20 patients received 4-44 (mean, 9.7) courses of CF-Mito over a period of 1.5-24 (mean, 5.3) months. The results obtained in these 20 patients with evaluable lesions included no complete remission (CR), 4 partial remissions (PRs), 9 cases of stable disease (SD), and 7 cases of progressive disease (PD). The PR duration was 1.5-22 (mean, 7.5) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, diarrhea, stomatitis, liver damage, and heart failure. In all, 11 patients received 3-7 (mean, 4.1) courses of PAM over a period of 3-14.5 (mean, 5.2) months. All 11 patients had evaluable lesions, and their responses included no CR, 5 PRs, 3 cases of SD, and 3 cases of PD. The PR duration was 1-3 (mean, 1.6) months. The side effects encountered in this group included anorexia, nausea, vomiting, myelosuppression, heart failure, and hair loss.
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PMID:Combination chemotherapy for advanced urothelial-tract carcinoma. 139 20

Five patients with severe pemphigus vulgaris refractory to conventional therapy with azathioprine and corticosteroids were treated with cyclophosphamide, vincristine and prednisone. One patient was not evaluable, while the remaining four patients showed a complete response. Duration of response was in the range of 13-94 months. Toxicity was mainly represented by alopecia, myelosuppression and gastrointestinal side-effects such as nausea/vomiting. Although cyclophosphamide and vincristine may induce severe side-effects, this association may be useful in controlling severe disease resistant to previous conventional therapies.
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PMID:Cyclophosphamide plus vincristine and prednisone in the treatment of severe pemphigus vulgaris refractory to conventional therapy. 140 72

Twenty patients with epithelial ovarian carcinoma were treated with high-dose cisplatin 200mg m-2. Patients were to receive three cycles at 21 day intervals. Treatment was stopped if severe myelosuppression or any neurotoxicity occurred. Overall, eight (40%) of patients responded with a complete response in five (25%). Four of 16 (25%) previously treated patients responded. The median duration of response was 44 weeks (range 6-130). In patients previously treated there was a significant association (P < 0.002) between response and a remission free interval of 52 weeks or more from primary chemotherapy. Toxicity was assessable in 18 patients. Alopecia and nausea/vomiting were common. Myelosuppression was recorded in nine patients delaying planned administration in eight of 35 cycles. Five patients developed anaemia and six thrombocytopenia. Neurotoxicity affected seven patients and varying degrees of tinnitus six patients. Neurotoxicity and myelosuppression were indications for cessation of treatment in 8 patients receiving less than three cycles. Analysis revealed no significant association between toxicity and prior cisplatin exposure, age or the amount of high-dose cisplatin administered. This series reveals that it is possible to achieve good response rates using high-dose cisplatin without encountering debilitating neurotoxicity.
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PMID:Single agent high-dose cisplatin (200 mg m-2) treatment in ovarian carcinoma. 141 13

This study was undertaken in order to evaluate the effect of intraperitoneal administration of CDDP on fourteen patients with peritoneal dissemination of advanced or recurrent gastric cancer. The procedure was used together specific hydration transfusion and diuretics. Two patients showed a complete response and 5 patients a partial response. Following this therapy, 2 patients have survived for more than 6 months. Alimentary symptoms (nausea, vomiting) were found but renal toxicity and serious myelosuppression were not recognized in all patients.
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PMID:[Intraperitoneal administration of cisplatin (CDDP) for advanced or recurrent gastric cancer with peritoneal dissemination]. 144 86


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