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)

From January 1978 to May 1983, 41 patients with primary high-grade osteogenic osteosarcoma of a limb were treated with a combination of intensive chemotherapy and prophylactic lung irradiation (PLI) intercalated between the first two cycles of chemotherapy. The primary tumor was treated according to its size and location by amputation, resection, high-dose radiotherapy, and salvage amputation for a tumor progressing under radiotherapy. Two weeks after surgery or simultaneously with radiotherapy, a three-drug regimen (cycle A) consisting of mitomycin C on day 1, vincristine followed by a 6-hour infusion of methotrexate on day 2 was given. Folinic acid rescue was started 6 hours after the end of the methotrexate infusion. A PLI of 20 G was given from day 10 to 22. On day 28, a four-drug regimen (cycle B) combining doxorubicin on day 1, vincristine on day 2 and dacarbazine with cyclophosphamide on days 3 to 6 was administered. Thereafter, five additional cycles of A and B were administered provided that the absolute number of polymorphonuclear cells and platelets had recovered. When these values were not attained, treatment was delayed until recovery. After a mean follow-up of 60.6 months, 16 patients have developed distant metastases, associated in four cases with local recurrence. Sixteen patients have died: 15 with metastases, one with no evidence of disease (toxic death). The overall survival of the entire group is 66% and the continuously disease-free survival 58% at 5 years. Alopecia, nausea, vomiting, asthenia, anorexia, and infraclinical and reversible impairment of lung ventilatory function were universal. A noticeable hematologic toxicity also was seen. One toxic death occurred after a pulmonary infection. Two patients developed cardiomyopathy. A multiparametic analysis of prognostic factors shows the very significant influence of age on treatment outcome. The continuous disease-free survival among the 17 patients younger than 15 years is 41% compared to 79% in older patients. The prognostic influence of age was independent of other factors. The delay (for more than two cycles) of methotrexate administration was the second independent prognostic factor. These results raise the question of using different protocols of adjuvant chemotherapy for patients younger or older than 15 years in order to optimize the curability/toxicity ratio.
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PMID:Age and dose of chemotherapy as major prognostic factors in a trial of adjuvant therapy of osteosarcoma combining two alternating drug combinations and early prophylactic lung irradiation. French Bone Tumor Study Group. 312 57

A number of reports have described enhanced therapeutic activity of 5-fluorouracil (5-FU) when combined with high-dose folinic acid (dl-CF). In the present phase-II study 35 patients with colorectal cancer were entered into a first-line chemotherapeutic protocol consisting of dl-CF 200 mg/m2 i.v. push directly followed by 340 mg/m2 5-FU i.v. pushon - days 1-5. Thus far a response rate of 37.5% (12 PR) has been achieved, and minor responses or no change were registered in 43.7% (14 MR or NC), lowering the rate of primary therapeutic failures to 18.8%. Median time to progression was 6.2 months. Toxic side effects consisted mainly of diarrhea, nausea and mucositis. As second-line therapy 5-FU/dl-CF and dipyramidole p.o. were administered to 10 patients with resulting 4 NC. Mitomycin C was given to 9 patients as a third-line regimen with resulting 5 NC for 2-4 months.
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PMID:[Sequential treatment of progressive metastatic colorectal cancer with 5-fluorouracil/folinic acid, dipyramidole and mitomycin C]. 314 43

Twenty-three patients with advanced colorectal cancer were treated with folinic acid (200 mg/m2/day 1-5 IV bolus injection) and 5-fluorouracil (400 mg/m2/day 1-5 IV in 15 minutes) every 28 days. Only three patients were pretreated. Objective response was observed in 6 (30%) of 20 evaluable patients (three complete and three partial responses). The median duration of response was 9 months (range 5-15) and time to disease progression ranged from 2 to 12 months (median 6 months). Median survival was 21 months (range 12-23+) for responders. Another 6 (30%) patients had stabilization of disease. Toxicity was generally gastrointestinal (mucositis, diarrhea, nausea); moderate leukopenia was noted. The response rate found in this study indicates that folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly in colorectal cancer.
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PMID:High-dose folinic acid and 5-fluorouracil in advanced colorectal cancer. 325 1

High-dose leucovorin (folinic acid) supplementation was tested in a prospective, unblinded manner for 4 weeks in 7 rheumatoid arthritis patients who were being treated successfully with low-dose methotrexate (MTX). Nausea caused by MTX disappeared; however, the underlying rheumatic disease worsened in all patients. Subjective clinical assessment, Ritchie articular index, grip strength, erythrocyte sedimentation rate, and levels of C-reactive protein showed statistically significant deterioration. All these parameters improved after the leucovorin was stopped. This is the first direct clinical evidence implying folate antagonism in the action of low-dose MTX therapy in rheumatoid arthritis patients.
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PMID:The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis patients. 326 Jul 83

An enhanced antineoplastic effect of 5-fluorouracil in patients with advanced colorectal cancer has been produced either by combination with folinic acid or administration by continuous infusion. Thirty-seven patients with advanced measurable colorectal cancer received high-dose folinic acid (LV 200 mg/m2) followed by 5-fluorouracil i.v. bolus (300 mg/m2) and continuous infusion (300 mg/m2) on days 1 and 2 then 14 and 15 every 4 weeks. In the absence of toxicity, 5-FU was increased to 400 mg/m2 i.v. bolus and continuous infusion at course 2 and to 500 mg/m2 at course 3 and from course 4 maintained at 500 mg/m2. Responses were: complete responses: 1 (2.7%), partial responses: 19 (51.4%), no change: 8 (21.6%) and progressive disease: 9 (24.3%). CEA decrease was correlated with response. Median duration of response was 11 months. Median survival was 18 months, 21% of the patients were alive at 2 years. Toxicity was low, with diarrhea in 17% and nausea in 11.5% of the patients. LV-5-FU bolus and continuous infusion is safe and has definite activity in metastatic colorectal cancer.
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PMID:High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer. 326 75

In a murine model system, folinic acid demonstrated host-protective properties during administration of repetitive and lethal doses of vincristine (VCR). Subsequently, folinic acid was evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 18 patients receiving folinic acid have been compared with those observed in 70 patients who previously received VCR without folinic acid in the same chemotherapy program. All patients ideally were intended to receive VCR 1.0 mg/m2 weekly for 6 weeks, with dose modification for neurotoxicity. Treatment patients received folinic acid 800 mg PO daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 7 (39%) treatment patients and 17 (24%) comparison patients (P = 0.21). The mean percentage of the ideal dosage of VCR was 73.7 +/- 28.7 in patients receiving folinic acid and 76.1 +/- 20.5 in those given only VCR (P = 0.69). Hematologic toxicities were similar in both groups, but nausea occurred more frequently in the folinic acid group. Folinic acid in this dose and schedule afforded no protection from the neurotoxic side effects of VCR.
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PMID:Clinical trial of folinic acid to reduce vincristine neurotoxicity. 348 49

The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in colorectal cancer (CC). Cisplatin is reported to have synergistic activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients who had previously received chemotherapy with FA + 5-FU and relapsed. Two months after the last dose of FA + 5-FU and documentation of relapse, patients continued with the regimen consisting of cisplatin 20 mg/m2 in 15 min i.v. infusion followed by FA 500 mg/m2 in 1 h i.v. infusion, in the middle of which 5-FU 500 mg/m2 i.v. bolus was administered, with adequate post-hydration. This was repeated weekly for 4 weeks followed by a 2 week rest, for a maximum of six cycles. A total of 30 patients with CC that had relapsed to the combination of FA + 5-FU were treated; 23 had previous surgery and none had radiotherapy. Local recurrence was found in eight patients, metastases in the liver in 21, in lymph nodes in six, lung six and peritoneal metastases in seven. Seven patients responded partially. Toxicity requiring dose reduction or discontinuation of treatment included neutropenia 42% (grade 3:7%), mucositis 28% (grade 1:2), diarrhea 63% (Grade 3:10%), nausea-vomiting 55% (Grade 3:10%), increased creatinine value in three patients and peripheral neuropathy in two patients. We conclude that evaluation of this regimen shows substantial toxicity, with satisfactory response as a second line chemotherapy in these heavily pretreated patients.
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PMID:5-Fluorouracil, folinic acid and cisplatin in advanced colorectal cancer: a pilot study. 757 65

We have conducted a retrospective study of high-dose folinic acid and 5-fluorouracil in 96 patients with advanced colorectal cancer. Patients received 200 mg m-2 (maximum 300-350 mg) folinic acid by infusion over 2 h followed by an i.v. bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 600 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for four cycles; thereafter patients with objective response continued to a maximum of eight cycles. The overall response rate was 10.6% in 85 evaluable patients. The median duration of response was 11 months. The median survival was 6 months. Toxicity was low, only one patient experiencing toxicity greater than WHO grade II (grade IV platelet toxicity). Diarrhoea, nausea, vomiting and mucositis also occurred but were mild and infrequent. Our low response rate may be related to factors such as patient characteristics or duration of treatment.
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PMID:High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer: poor response rate in unselected patients. 766 93

Interferon alpha-2a (IFN-alpha) and folinic acid (FA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. A phase II study was initiated to evaluate the effect of a combination of 5-FU/FA/IFN-alpha in patients with advanced pancreatic cancer. Sixty previously untreated patients with advanced adenocarcinoma of the pancreas were treated with 500 mg m-2 FU via an intravenous bolus 1 h after the initiation of a 2 h infusion of 500 mg m-2 FA. Before starting the FA infusion, 6 million units (MU) of IFN-alpha was administered subcutaneously. The treatment was repeated once a week. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR) and 28 (49%) no change of disease (NC). Thirteen patients (23%) had progressive disease (PD). The median survival time was 10 months for all patients, 22 months for patients with partial remission and 5 months for patients with progressive disease. Many patients with tumour-related pain whose tumours were affected in terms of PR, MR, NC were free of pain during treatment with this regimen (22/36 patients). The common toxicities observed were fever (56%), nausea (37%) and diarrhoea (33%). These data suggest that biochemical modulation of 5-FU with FA and IFN-alpha has some positive effects in the treatment of pancreatic cancer of moderate toxicity.
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PMID:Treatment of advanced pancreatic cancer with 5-fluorouracil, folinic acid and interferon alpha-2A: results of a phase II trial. 781 23

1. The pharmacokinetics and toxicity of racemic 5-methyltetrahydrofolic (rac-5-MTHF) acid after i.v. infusion were investigated in 18 patients with advanced colorectal cancer. Doses of 100-600 mg rac-5-MTHF/m2 were administered over 2 h together with a bolus of 500 mg/m2 5-fluorouracil (5-FU) as a midpoint injection. 2. The pharmacokinetics of both diastereoisomers were linear in the range from 100-600 mg 5-MTFH/m2. Independent of the administered dose, the maximal plasma concentration of [R]-5-MTHF was nearly twice that of [S]-5-MTHF. The elimination of [S]-5-MTHF from plasma was considerably faster than that of the [R]-isomer (elimination half-life: 3.1 +/- 1.0 h vs 8.3 +/- 3.2 h). No metabolites were detected in plasma and in urine samples. 3. The plasma protein binding was stereoselective ([R]-5-MTHF bound: 88.2 +/- 2.7%; [S]-5-MTHF bound: 59.9 +/- 6.8%; P < 0.001), causing a significantly higher renal clearance for [S]-5-MTHF when compared with the [R]-isomer (37.5 +/- 23.7 ml min-1 vs 12.7 +/- 11.2 ml min-1, P < 0.001). There was no dose dependence, but gender influenced renal clearance (CLren[R]-5-MTHF: male vs female: 20.5 +/- 14.5 ml min-1 vs 7.8 +/- 4.7 min-1, P = 0.03; CLren [S]-5-MTHF: male vs female: 57.2 +/- 21.7 ml min-1 vs 25.7 +/- 16.2 ml min-1, P = 0.006). 4. Toxic side effects of the combination 5-FU/5-MTHF were rare and generally mild, and included stomatitis, nausea/emesis, diarrhoea, anaemia, leukopenia, and thrombocytopenia. 5. In combination with 500 mg 5-FU/m2 a single dose of 600 mg rac-5-MTHF/m2 can safely be administered to patients with colorectal cancer. A similar therapeutic benefit of 5-MTHF to folinic acid in the biochemical modulation of 5-FU is supported by the comparison of in vitro and in vivo data.
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PMID:Stereospecific pharmacokinetics of rac-5-methyltetrahydrofolic acid in patients with advanced colorectal cancer. 852 81


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