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)

A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities, and the response rate of irinotecan administered weekly with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, surgically unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled. Irinotecan was administered as a 90 min intravenous infusion once weekly for 6 weeks. The starting dose was 30 mg m(-2) and dose escalation was done in 15 mg m(-2) increments. Dose-limiting toxicity was defined as grade 3 nonhaematologic toxicity (excluding nausea, vomiting and alopecia) or grade 4 haematologic toxicity according to the WHO criteria. Radiation was delivered to the primary tumour and regional lymph nodes (40 Gy), followed by a boost to the primary tumour (20 Gy). Twenty-seven patients were entered into this study at three irinotecan dose levels (30, 45 and 60 mg m(-2)). Twenty-six eligible patients were evaluated for toxic effects and clinical outcome. Severe oesophagitis, pneumonitis, and diarrhoea occurred at 45 and 60 mg m(-2). Three of the five patients given 60 mg m(-2) developed grade 3 or 4 oesophagitis and pneumonitis. In addition, one patient died of pneumonitis after completing therapy at 45 mg m(-2) in the phase II study. The objective response rate was 76.9% (95% CI, 53.0-88.9%). Oesophagitis, pneumonitis, and diarrhoea are the dose-limiting toxicities of weekly irinotecan combined with thoracic irradiation. The maximum tolerated dose and the dose for the phase II study were 60 and 45 mg m(-2) wk(-1), respectively. This combined therapy for locally advanced non-small cell lung cancer is promising and shows acceptable toxicity.
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PMID:Phase I/II study of weekly irinotecan and concurrent radiation therapy for locally advanced non-small cell lung cancer. 1018 91

This article provides guidelines for the use of amifostine (Ethyol, Alza Pharmaceuticals, Palo Alto, CA, and U.S. Bioscience, Inc., West Conshohocken, PA), a pancytoprotective agent approved for reducing renal toxicity associated with cisplatin administration in patients with advanced ovarian or non-small cell lung cancer. Pretreatment with amifostine reduces the incidence of serious and cumulative chemotherapy-induced toxicities, thus improving quality of life, and allows administration of optimal doses and scheduling of chemotherapy and radiation therapy, translating into improved survival. Practical guidelines for administration of amifostine are provided in an effort to ameliorate emesis, amifostine's principle side effect.
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PMID:Administration of the cytoprotectant amifostine. 1023 50

This phase I study was performed to assess the feasibility of combining cisplatin/etoposide (VP-16) with the arotinoid Ro 40-8757 and to determine the dose-limiting toxicity (DLT) of Ro 40-8757 in this combination. Patients with non-small cell lung cancer were eligible. Treatment consisted of Ro 40-8757 p.o. day 1-21, cisplatin 100 mg/m2 i.v. on day 2 and VP-16 100 mg/m2 i.v. on day 2-4, repeated every 3 weeks. Eighteen patients were evaluable for toxicity and response. The doses of Ro 40-8757 ranged from 84 mg/m2 once daily to 42 mg/m2 thrice daily (tid). DLT consisting of delayed nausea/vomiting was reached at 42 mg/m2 tid. Consequently, the maximum tolerated dose was set at one dose level below the DLT, i.e. 28 mg/m2 tid. Skin toxicity occurred but was well manageable. Pharmacological analyses showed a small increase in the volume of distribution of cisplatin and VP-16 between the first and third course. However, no relationship with side effects was found. A response was achieved in 50% of patients. The combination of cisplatin/VP-16 with Ro 40-8757 appears to be feasible at a dose schedule of 28 mg/m2 tid. The response rate was at the upper rate of what can be expected with cisplatin and VP-16.
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PMID:Phase I and pharmacologic study of the arotinoid Ro 40-8757 in combination with cisplatin and etoposide in patients with non-small cell lung cancer. 1037 70

To determine the activity and toxicity of gemcitabine in non-small cell lung cancer, three phase II studies of single agent gemcitabine have been conducted between 1990 and 1994. In an early phase II study, gemcitabine was administered of 800 mg/m2 on day 1, 8, 15 every four weeks (step I), and 1,000 mg/m2 (step II). Response was observed in 3 of 13 patients with previously untreated non-small cell lung cancer, although there was no responders in the previously treated patients. Late phase II studies were performed at 20 (group A) and 24 (group B) Japanese institutions to confirm the efficacy and safety of gemcitabine administered alone in patients with non-small cell lung cancer. Seventy-three patients (group A) and 67 patients (group B) were entered into these studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response in group A. Of 67 patients, 14 (20.9%) showed a partial response in group B. Grade 3 or greater toxicities included anemia (20.5%) and leukopenia (9.6%) in group A, and in 13.4% and seven 10.4% in group B, respectively. And grade 3 thrombocytopenia was observed in 1.4%. Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of ARDS. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility in advanced non-small cell lung cancer on an outpatient basis. Further trials in combination with other active agents are warranted.
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PMID:[Phase II studies of gemcitabine for non-small cell lung cancer in Japan]. 1039 14

The combination Phase I study of gemcitabine hydrochloride with cisplatin was conducted in the patients with non-small cell lung cancer (NSCLC) at 5 investigation sites. Gemcitabine was administrated on day 1, 8 and 15 and cisplatin on day 1 of each 28-day cycle. The dosage of cisplatin was fixed to 80 mg/m2 and the dosage of Gemcitabine was gradually escalated in 3 dosing level from 600, 800 to 1,000 mg/m2. The maximum tolerated dose (MTD) and the recommended dose was determined with Continual Reassessment Method. For each dose level, 6 cases, 3 cases and 6 cases were registered respectively and all 15 cases were evaluable. In the dose level 3 with 1,000 mg/m2 of gemcitabine and 80 mg/m2 of cisplatin, grade 4 neutropenia was observed as DLT in 3 out of 6 cases, thus dose level 3 was considered as MTD and the recommended dose. Major adverse events were leukopenia, neutropenia, nausea/vomiting and anorexia. The incidence of such adverse events seemed to be dose-dependent and especially the grade of neutropenia seemed to be more serious as the dose increased. Also, the grade of liver function tests abnormal seemed to be more serious as the dose increased but the incidence as well as the grade did not have tendency of dose-dependent in another events including renal function tests abnormal. On the other hand, as to the efficacy PR was observed in 4 out of 15 cases. Based upon the results, it is necessary to discuss further the efficacy in the recommended dose in the combination therapy of gemcitabine and cisplatin.
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PMID:[Phase I study of gemcitabine hydrochloride (LY 188011) combination therapy with cisplatin in the patients with non-small cell lung cancer]. 1039 16

Clinical study has been conducted to evaluate the efficacy of chemotherapy with docetaxel and cisplatin in six patients with advanced non-small cell lung cancer. Treatment schedule consisted of docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 and repeated every 4 weeks. Eligible patients had histologically proven locally advanced or metastatic non-small cell lung cancer, PS < or = 2, age < or = 74, normal hematological, hepatic and renal functions and informed consent in writing. Six patients have been included; all were males, median age 64 (range 47-74), histology; adenocarcinoma 4, squamous cell carcinoma 2, stage III B 4, stage IV 2. Among these 6 patients, 3 PR (50%) were observed. Neutropenia was the most common adverse event (83%). The lowest granulocyte counts were most frequently seen on day 9.4 (range: 6-14). Non hematologic adverse events included alopecia (6 cases), general fatigue (5 cases), anorexia (5 cases) and emesis (3 cases). These events were recovered rapidly with no therapy. The results suggest that combination chemotherapy of docetaxel and cisplatin will be effective and safe under careful observation.
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PMID:[Evaluation of chemotherapy with docetaxel and cisplatin in advanced non-small cell lung cancer]. 1039 19

Preventive combined administration of granisetron 3 mg, methylprednisolone 500 mg, and metoclopramide 40 mg decreased the post-chemotherapy emesis from 56% in 68 control cases to 16% in 31 administered cases. All cases had non-small cell lung cancer and were treated with cisplatin 80 mg/m2, vindesine 3 mg/m2, and mitomycin C 8 mg/m2. YG character test in 23 cases revealed that emotional unstableness, characterized by the coupled rightward shift of the N (nervous) and I (inferior complex) components, was the important cause of emesis in those patients who failed to respond to the anti-emetic drugs shown above. Anti-emetic agents with different mechanisms and psychiatric counseling are needed in these emotionally unstable patients.
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PMID:[Anti-emetic treatment for patients with non-small cell lung cancer after chemotherapy, usefulness of preventive combination of anti-emetic agents and importance of psychiatric aspect of patients]. 1041 Jan 51

Between September 1994 and July 1997, 78 patients with advanced/metastatic, non-small cell lung cancer (NSCLC) were selected for the NIP (vinorelbine, ifosfamide, and cisplatin) protocol. The study group included 43 males; age range 34-74 years; median age 56 years; median follow-up for all patients was 14 months and for surviving patients, 30 months. Histological distribution included 55 adenocarcinomas (70.5%), 8 squamous cell carcinomas, and 9 large cell carcinomas. Stage distribution was 14 stage IIIB (malignant effusions) and 64 stage IV or recurrent metastatic; sites of metastasis were lungs, -26; liver-19; bones-27; brain-7; adrenals-3; distant nodes-2; skin-2. The NIP regimen was well tolerated by most of the patients but nausea/vomiting was noted in 55% of the cycles administered, most of them of grade 1-2 severity. Fifteen neutropenic episodes (5%) were encountered. Response to NIP was: 44 partial responses (56%); 1 complete response (1%); overall response, 58%. For stage IIIB, overall response was 36%, while for stage IV/metastatic, overall response was 63%. The median time to progression was 7 months for stage IIIB and 8 months for stage IV/metastatic disease and the overall median survival achieved was 14 months, with 60% of patients alive after one year. No significant difference in survival outcome was noted between patients with metastatic disease and those with stage IIIB (malignant effusion) disease. The NIP regimen has produced encouraging results in advanced NSCLC, as well as a favourable toxicity profile. The efficacy of NIP as a palliative tool should be assessed. A randomized trial to compare NIP with a two-drug combination of vinorelbine and cisplatin has been initiated.
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PMID:Vinorelbine, ifosfamide and cisplatin in advanced non-small cell lung cancer. 1042 51

Temozolomide (TMZ) is an oral imidazotetrazinone that is spontaneously converted to 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC) at physiological pH. MTIC methylates DNA at the O6 position of guanine, although this lesion may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (AGAT). In this study, TMZ was combined with cisplatin (CDDP), because both agents have single-agent activity against melanoma and other tumor types. Additionally, CDDP has been shown to inactivate AGAT, and subtherapeutic concentrations of CDDP have been shown to increase the sensitivity of leukemic blasts to TMZ. This Phase I study sought to determine the toxicities, recommended dose, and pharmacological profile of the TMZ/CDDP combination. Patients were treated with oral TMZ daily for 5 consecutive days together with CDDP on day 1 (4 h after TMZ) every 4 weeks at the following TMZ (mg/m2/day)/CDDP (mg/m2) dose levels: 100/75, 150/75, 200/75, and 200/100. Plasma samples were obtained on days 1 and 2 to evaluate the pharmacokinetic parameters of TMZ alone and in combination with CDDP. Fifteen patients received a total of 44 courses of TMZ/CDDP. The principal toxicities of the regimen consisted of neutropenia, thrombocytopenia, nausea, and vomiting, which were intolerable in two of six new patients treated at the 200/100 mg/m2 dose level. Of five patients receiving 17 courses at the next lower dose level (200/75 mg/m2), none experienced dose-limiting toxicity. Antitumor activity was observed in patients with non-small cell lung cancer, squamous cell carcinoma of the tongue, and leiomyosarcoma of the uterus. Pharmacokinetic studies of TMZ revealed the following pertinent parameters (mean +/- SD): time to maximum plasma concentration (Tmax) = 1.1+/-0.6 h (day 1) and 1.7+/-0.9 h (day 2); elimination half-life (t1/2) = 1.74+/-0.22 h (day 1) and 2.35+/-0.70 h (day 2); and clearance (Cl(s)/F) = 115+/-27 ml/min/m2 (day 1) and 141+/-109 ml/min/m2 (day 2). TMZ drug exposure, described by the area under the plasma concentration-time curve (AUCinfinity) and the maximum plasma concentration (Cmax), was similar on days 1 and 2. On the basis of these results, the recommended doses for Phase II clinical trials are TMZ 200 mg/m2/day for 5 days with 75 mg/m2 CDDP on day 1, every 4 weeks. The addition of CDDP did not affect the tolerable dose of single-agent TMZ (200 mg/m2/day x 5 days), nor did it substantially alter the pharmacokinetic behavior of TMZ.
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PMID:A Phase I and pharmacokinetic study of temozolomide and cisplatin in patients with advanced solid malignancies. 1043 61

We conducted a randomized phase II trial of two different schedules of topotecan in patients with advanced-stage non small lung cancer (NSCLC) without prior cytotoxic chemotherapy. All patients had histologic or cytologic confirmation of stage IV (M1) or III-B NSCLC. Patients were stratified by performance status, stage and weight loss. Patients were randomized to receive topotecan at intravenous doses of 1.5 mg/m(2)/day over 30 min for 5 days every 3 weeks (Arm A) or 1.3 mg/m(2)grade 3 in both arms included leukopenia, thrombocytopenia, malaise, constipation, diarrhea, lethargy, pulmonary, vomiting, infection and myalgia. Severe (> or = grade 3) thrombocytopenia occurred in 15.8% of Arm A patients and 37.8% of Arm B patients and this difference was statistically significant (P=0.03). The median times to progression are 101 and 63 days (P=0. 75) and the median survival times are 257 and 179 days (P=0.83) for Arms A and B, respectively. These differences in time to progression and overall survival are not statistically significant. Topotecan has limited, single agent activity in advanced NSCLC when given as 1. 5 mg/m(2)/day over 30 min for 5 days every 3 weeks. We do not intend to pursue further investigations with topotecan in patients with NSCLC.
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PMID:A randomized phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung cancer. 1071 33


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