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)

Carboplatin/etoposide is an active regimen in the treatment of small cell lung cancer. This phase II trial evaluated whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to this two-drug combination might increase its efficacy. Since April 1996, 55 patients were entered into the ongoing protocol. To date, 35 patients are evaluable for efficacy and toxicity. Most of the evaluable patients are male (28). The patients' median age is 60 years (range, 36 to 74 years); 32 patients have Eastern Cooperative Oncology Group performance status ratings of 1, and the balance are Eastern Cooperative Oncology Group performance status 0. All patients had limited-stage disease. Patients received paclitaxel 175 mg/m2 via 1-hour intravenous infusion on day 1, carboplatin dosed to an area under the concentration-time curve of 5, also on day 1, and oral etoposide 100 mg on days 2 through 8. Overall, 31 patients responded to paclitaxel/carboplatin/etoposide therapy, including complete response in 13 patients (37.1%) and partial response in 18 patients (51.4%). Disease was stable in three patients (8.6%) and disease progressed in one (2.0%). Hematologic toxicity included neutropenia (World Health Organization grade 3 in 24.1% of patients, grade 4 in 31.3%), anemia (4% grade 3, no grade 4), and thrombocytopenia (3.2% grade 3, 2.1% grade 4). Nonhematologic adverse events included minor nausea/vomiting (1.5% grade 3, 9.2% grade 2), polyneuropathy (2.3% grade 2, 17.5% grade 1), and myalgia/arthralgia (8.2% grade 2, 16.4% grade 1). Paclitaxel/carboplatin/etoposide is active in small cell lung cancer with moderate toxicity and good subjective tolerance. There were no life-threatening hematologic or nonhematologic complications in this phase II trial.
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PMID:Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. 933 Nov 41

Our objective was to determine the maximum tolerated dose of cyclosporin A (CsA) delivered as a loading dose (LD) and continuous i.v. infusion (CI) in combination with carboplatin in patients with refractory gynecologic cancers. Twenty-nine heavily pretreated patients (25 ovarian epithelial, 2 cervical, and 2 endometrial carcinomas) received 113 cycles of CsA and carboplatin from September 1989 to September 1991. Twenty-four of these 29 carcinomas were strictly defined to be platinum resistant. CsA was administered as a LD escalated from 6 to 10 mg/kg followed by a 24-h CI from 2.5 to 14.5 mg/kg/day. Carboplatin was targeted to an area under the time versus concentration curve (AUC) of 6 mg/ml x min and was not dose escalated. Whole-blood CsA concentrations (fluorescence polarization immunoassay) at the maximum tolerated dose (10 mg/kg LD, 14.5 mg/kg/day CI) ranged from 2.4 to 3.0 microgram/ml over 12 h. Estimated median carboplatin AUC, based on calculated carboplatin clearance, was 7.9 mg/ml x min. The dose-limiting toxicity of the combination of CsA and carboplatin was grade 4 thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 35% of the patients, which could be explained by the effects of carboplatin (AUC of 6 mg/ml x min) alone. Overall, neutropenia occurred in 24% of the patients and anemia in 17% of the patients. Grade 3 or 4 nausea or vomiting was noted in 10 and 14% of the patients, respectively. Grade 3 hypertension during CsA administration occurred in 14% of the patients. No grade 3 or 4 nephrotoxicity was seen in this trial. Three objective responses were noted: one complete response (11 months) and one partial response (5 months), both in potentially platinum-sensitive patients with platinum-free intervals of only 9 months each. One platinum-resistant patient had a partial response for 21 months. Five additional patients experienced >75% reduction of CA-125 or a return to a normal CA-125 titer. We concluded that whole-blood CsA concentrations of >3.0 microgram/ml (as seen when CsA is used as a modulator of multidrug resistance) were not achievable in this combination with carboplatin in this population of heavily pretreated gynecologic cancer patients. However, because CsA is used in this trial as a chemosensitizer in platinum-sensitive tumors and as a chemomodulator of platinum resistance, we targeted a CsA concentration of >1.0 microgram/ml, which was achieved. The CsA dose recommended for a Phase II trial of this combination is 10 mg/kg LD and 11.6 mg/kg/day CI, which results in blood CsA concentrations ranging from 1.2 to 1.3 microgram/ml over 12 h. Responses in this population of refractory gynecologic cancer patients are unusual, and these encouraging results form the basis for a Phase II trial of this combination.
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PMID:Phase I trial of intravenous carboplatin and cyclosporin A in refractory gynecologic cancer patients. 981 19

Between 1/1990-8/1997 two courses of single agent Carboplatin had been given to 36 patients with clinical stage I seminoma. Within an median follow up period of 52 months (17-88) 29 out of 34 patients were analyzed retrospectively. During this period no recurrences had been noted and nobody of our patients died (0% relapsrate, 100% survival-rate). The Carboplatin-therapy was well tolerated. Myelosuppression after chemotherapy was mild (WHO grade I). The experienced acute toxic side effects (max. grade II WHO) during and after chemotherapy had been nausea (37%), vomiting (14%) and mild hairloss (11%). Until now no long term side effects were noticed. A standardized questionnaire had been used to evaluate the impairment of quality life after single agent carboplatin therapy. After a minimum of one year follow up averagly 79% (62-92%) of the asked patients showed no impairment of their quality of life, whereas 19% (8-38%) of the people experienced mild impairment of their quality of life. Because of the shown low recurrence rate, the minimal toxicity and no relevant impairment of the quality of life single agent carboplatin therapy will be an alternative approach for clinical stage I seminoma.
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PMID:[Carboplatin monotherapy in clinical stage I of seminoma. An acceptable alternative?]. 988 92

RMP-7, a nine amino acid peptide bradykinin agonist, increases the delivery of hydrophilic compounds across the blood-tumour barrier. In this dose ranging study, 14 patients with progressing malignant glioma (9 glioblastoma multiforme, 4 anaplastic astrocytoma, 1 anaplastic oligodendroglioma; age range 31-68 years, baseline Karnofsky range 60-90%, 5 having had prior chemotherapy) were treated with intravenous RMP-7 and carboplatin to assess the safety, tolerability, and side-effect profile of increasing doses of this combination. Carboplatin dosing was by target area under the curve (AUC) according to the Calvert protocol. Patients were allocated to one of five treatment regimes: cohort A (n = 2) received 50 ng/kg RMP-7 and target AUC 5 mg/ml/min carboplatin; cohort B (n = 3) 100 ng/kg RMP-7 + AUC 5; cohort C (n = 2) 100 ng/kg RMP-7 + AUC 7; cohort D (n = 2) 200 ng/kg RMP-7 + AUC 7; cohort E (n = 5) 300 ng/kg RMP-7 + AUC 7. Treatment was given once every 4 weeks with magnetic resonance imaging scans every 2 months. Patients received 37 cycles in total (median 2, range 1-7). The drug combination, as a cancer treatment, was tolerated in all groups. Effects possibly related to RMP-7 included flushing, nausea, headache and mild increase in heart rate, all transient. 3 patients in cohort E experienced grade 3/4 neutropenia and thrombocytopenia. These toxicities are consistent with known effects of carboplatin at this dose range. In cohort E (n = 5) 1 patient improved and another remained stable for > or = 6 months. In summary, the dose was escalated to the maximum dose of RMP-7 given to volunteers without additional related side-effects. The side-effects of the combination were consistent with giving the two drugs alone and would merit further study for efficacy.
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PMID:A phase I study of intravenous RMP-7 with carboplatin in patients with progression of malignant glioma. 989 73

The effects of oral antiemetic drugs on delayed emesis induced by emetogenic chemotherapy were studied in seventeen patients (43 courses) with gynecological malignancies. On day 1, all patients received intravenous granisetron (40 micrograms/kg) and methylprednisolone (250 mg/body) for the control of acute emesis 0-24 hrs after receiving CDDP or CBDCA. Then they received each oral maintenance drug (dexamethasone 4 mg/day, ondansetron 4 mg/day and metoclopramide 40 mg/day) for the control of delayed emesis from day 2 to day 5. Efficacy rates for delayed emesis were 82.4% in dexamethasone, 75.0% in metoclopramide and 50.0% in ondansetron. The complete response for delayed nausea was 88.5% in metoclopram ide, and the complete response for delayed anorexia of 64.7% in dexamethasone was higher than for other oral drugs. The results suggest the usefulness of oral antiemetic therapy of dexamethasone plus metoclopramide or ondansetron for delayed emesis induced by cancer therapy.
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PMID:[Clinical studies of oral antiemetic drugs on delayed emesis induced by cancer chemotherapy]. 998 7

We investigated the efficacy of combination of ondansetron hydrochloride injection and tablet against nausea and vomiting in 22 lung cancer patients (total number of chemotherapy courses: 23) receiving chemotherapy of single-dose carboplatin (CBDCA) at a dose of 302.2 +/- 31.9 mg/m2. For suppressing emesis, the patients were given 4 mg of ondansetron injection on the day of CBDCA injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 5. The following results were obtained 5 days after the administration of carboplatin. 1) Control of nausea graded 'Good' or better counted for 95% or higher of all cases for each day of the chemotherapy. A complete nausea suppression rate was seen in 91.3%, 81.0%, 71.4%, 63.6% and 71.4% from Day 1 to Day 5, respectively. 2) Control of vomiting graded 'Major' control or better was achieved in 95% or more of all cases, for each day. The complete vomiting suppression rate observed from Day 1 to Day 5 was 91.3%, 78.3%, 65.2%, 69.6% and 91.3%, respectively. 3) Inhibitory effect on nausea and vomiting for each day of Days 1 to 5 graded as 'Effective' or better was shown in 90% or higher of all cases; based on overall judgement for Days 1 to 5, all cases were graded as 'Effective' or better. 4) The proportion of cases which was evaluated as 'Can eat most of the meal' was 88.0%, 73.9%, 50.7%, 50.7% and 65.2% from Days 1 to 5, respectively, against 95.7% prior to the start of chemotherapy. 5) No adverse drug reaction or abnormal clinical laboratory values were seen along with ondansetron. 6) In conclusion, combined treatment with ondansetron injection and tablet was considered clinically useful in control of nausea and vomiting during administration of carboplatin, and may also be useful for out-patient chemotherapy.
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PMID:[Effect of ondansetron hydrochloride injection and tablet against nausea and vomiting in lung cancer patients receiving carboplatin]. 998 8

A pilot study was performed to evaluate the feasibility and efficacy of irinotecan hydrochloride (CPT-11) plus carboplatin (CBDCA) for treatment of advanced or recurrent colorectal cancer. Fifteen patients with colorectal cancer (nonresectable, 1; noncurative resection, 5; recurrent disease, 9) were treated with CPT-11 (40-50 mg/m2) plus CBDCA (70-100 mg/m2) once a week for 2-3 weeks followed by a one-week rest. This treatment was repeated until disease progression or severe toxic effects were found. The total dose of CPT-11 ranged from 135 to 1,214 (median, 467) mg/m2 and that of CBDCA ranged from 267 to 2,022 (median, 933) mg/m2. Adverse effects included nausea (grade 2) in 2 (13.3%) diarrhea (grade 2) in 2 (13.3%), leukopenia (grade 3) in 2 (13.3%), thrombocytopenia (grade 1) in one (6.7%), and hair falling (grade 3) in one (6.7%). The response rate of 14 evaluable patients was 14.3% (CR, 1; PR,1; NC,7; PD,5). The median survival time of all patients was 405 days from the start of chemotherapy. The survival time of patients with CR, PR, and NC (n = 9) tended to be longer than that of those with PD (n = 5) (p = 0.06). The median time to disease progression was 105 days. These results suggest that this combination chemotherapy is feasible and effective in the treatment of advanced or recurrent colorectal cancer.
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PMID:[Combination chemotherapy with irinotecan hydrochloride plus carboplatin for patients with advanced or recurrent colorectal cancer--a pilot study]. 1096 97

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.
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PMID:Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer. 1244 53

A 73-year-old male underwent lobectomy with ND2a lymph node dissection and resection of the superior vena cava for right lung cancer in December 1998 at Akita University Hospital. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT4 (SVC) N2M0, Stage IIIB). He received 1 course of a combination of cisplatin (CDDP) and etoposide (ETP) as postoperative adjuvant therapy. In March 2001, he again underwent partial resection of the right lung (S8) due to recurrence. In December 2001, a new left lung metastatic tumor was found. The patient was transferred to our hospital, where he was given 1 course of vinorelbine (NVB) 25 mg/m2 (day 1, 8) and CDDP 80 mg/m2 (day 1). Subsequently, he received 2 courses of vinorelbine (NVB) 25 mg/m2 (day 1, 8) and carboplatin (CBDCA) 430 mg/body (day 1). After the chemotherapy, a complete response (CR) of metastatic lesions was achieved. Adverse reactions were grade 3 neutropenia, grade 2 alopecia and grade 1 nausea/vomiting. The combination of vinorelbine and platinum agent (CDDP/CBDCA) is a useful regimen in treating recurrent non-small-cell lung cancer.
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PMID:[A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin/carboplatin]. 1289 14

Irinotecan (CPT-11), a topoisomerase I inhibitor, has been shown in preclinical studies to be a potent radiosensitizer. Carboplatin, a known radiosensitizer with single-agent activity in non small-cell lung cancer (NSCLC), is felt to be a rational choice in combination with irinotecan. We have completed the initial portion of a phase I study, in patients with locally unresectable lung cancer, combining irinotecan with thoracic radiation. Thirteen patients have been entered onto this study through three dose levels (30 to 50 mg/m2/week) of irinotecan. There were seven partial responses in 12 evaluable patients, for an over-all response rate of 58%. Nausea, vomiting, and esophagitis were the principal toxicities of weekly irinotecan and concurrent thoracic radiation. As the maximum tolerated dose (MTD) of irinotecan with radiation has been established at 40 mg/m2/week, we are currently accruing patients to the second phase of this study with the addition of carboplatin (AUC = 2). Thus far toxicity has primarily been esophagitis.
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PMID:A phase I trial of outpatient weekly irinotecan/carboplatin and concurrent radiation for stage III unresectable non small-cell lung cancer: a Vanderbilt-Ingram Cancer Center Affiliate Network Trial. 1473 37


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