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

After informed consent 21 patients with advanced head and neck cancer resistant to folinic acid/5-fluorouracil (FA/5FU + cisplatin) were treated with weekly FA/5FU plus low dose hydroxyurea (HU) to evaluate if HU could further modulate 5FU antineoplastic activity. Five patients achieved a partial response (23.8%) which was short-lived (mean duration 6.5 months). Three patients (14%) had stable disease and 13 (62%) progressed. Among responders, four patients had epidermoidal carcinoma and one had clear cell carcinoma. Treatment was well tolerated and 5FU-related toxicity was not apparently worsened by the addition of HU. The most frequent toxicities were nausea/vomiting (81%), diarrhea (52%) and leukopenia (57%). Grade 3 nausea/vomiting and leukopenia were recorded in only 19 and 9% of cases, respectively. One patient had grade 1 cutaneous toxicity and a second patient showed a hand-foot syndrome. These results suggest that HU may further positively modulate 5FU antineoplastic activity.
 ...
PMID:Hydroxyurea modulates 5-fluorouracil antineoplastic activity in advanced head and neck carcinoma pretreated with chemotherapy. 142 29

From April 89 to October 90, 41 patients operated for a Dukes B or C colorectal cancer were randomized to receive 6 courses of adjuvant treatment with (A) 5-FU alone (440 mg/m2 IV bolus 5/21 days) or (B) folinic acid (200 mg/m2 IV bolus 5/21 days) preceding 5-FU (370 mg/m2 in short infusion 5/21 days). Ten patients received also one course of immediate post-operative continuous portal infusion (5-FU 500 mg/m2/day x 7 followed by a 2 hours infusion of mitomycin C 10 mg/m2). The portal treatment was well tolerated (1 case of GI tract disturbances, 1 catheter obstruction). The toxicity of adjuvant systemic treatment was evaluated on 232 courses (125 A, 107 B). Hematologic and skin toxicities, alopecia and nausea-vomiting were mild. The limiting toxicities (expressed as percentages of courses) were stomatitis (grades 2-3: 11.4% A; 22.6% B) and diarrhea (grades 3-4: 7.3% A; 14.2% B; one toxic death was to deplore in arm B from a grade 4 diarrhea). The pilot study has demonstrated the feasibility of the adjuvant treatment proposed; a multicentric randomized trial (expected accrual: 800 patients) has therefore been activated on 11.01.90; all patients will also receive levamisole while radio-therapy will be mandatory for rectal cancer.
 ...
PMID:[Tolerance of adjuvant treatment combining postoperative intraportal chemotherapy and a systemic treatment based on 5-fluorouracil in colorectal carcinoma with a histologically poor prognosis]. 146 46

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) daily for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridine, a new fluoropyrimidine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64%), lung (35%), local recurrence (10%) and peritoneum (10%). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxifluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.
 ...
PMID:Reversal of resistance to doxifluridine and fluorouracil in metastatic colorectal cancer: the role of high-dose folinic acid. 146 82

Preclinical data suggest that folinic acid as well as interferon alpha-2b may enhance the antitumor activity of 5-fluorouracil (5-FU). In a phase I trial, we recently showed that interferon alpha-2b (IFN), folinic acid and 5-FU can be safely administered with a 4-hour infusion of 5-FU. We therefore initiated a phase II trial evaluating the efficacy and safety of these three drugs. Forty-five evaluable patients with advanced metastatic colorectal cancer, documented progressive disease, and previously unexposed to chemotherapy were treated with sequential IFN 5 MU/d subcutaneously and folinic acid 200 mg/m2/d as bolus on days 1 to 7 followed by 5-FU in a 4-hour infusion at a dose of 500 mg/m2/d, resulting in a total dose of 3,500 mg/m2/course. This schedule was repeated on day 21. A total of 204 courses of therapy were completed. One of 45 patients (2%) achieved a complete response, and 13 of 45 patients (29%) achieved a partial response. An additional 16 patients (36%) had stable disease. The median time to disease progression was seven months (2 to 24 months). Despite the relatively high-dose intensity of 5-FU, toxicity was very mild. Grade 3 or 4 myelosuppression, stomatitis, and nausea/vomiting occurred in only three of 45 patients (7%). Four of 45 patients (9%) suffered from severe (grade 3/4) diarrhea. Neurotoxicity and infections of grade 2 to 4 did not occur. From these data we conclude that modulation of 5-FU with both folinic acid and IFN induces an overall response rate of 31% in disseminated colorectal cancer. Using a 4-hour application schedule of 5-FU, the therapeutic index can be improved even for high-dose intensity and requires further evaluation in combination with other modulators.
 ...
PMID:A phase II trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma. 155 76

A phase I study was undertaken in order to establish the maximum tolerated dose of intra-hepatic arterial 5-fluorouracil (5-FU) when given in combination with systemic folinic acid. Patients with colorectal liver metastases (n = 10) received escalating doses of 5-FU as a 24 h infusion with a fixed dose (400 mg m-2) of intravenous folinic acid once per week. Dose limiting toxicity (WHO grade greater than 2) was encountered at 2 g m-2 5-FU. Principal adverse effects were diarrhoea, vomiting and oral ulceration. The recommended dose for phase II studies is 1.5 g m-2 week-1 24 h 5-FU regional infusion with 400 mg m-2 week-1 intravenous folinic acid.
 ...
PMID:A phase I study of regional 5-fluorouracil and systemic folinic acid for patients with colorectal liver metastases. 161 63

A group of 60 patients with advanced head/neck cancer were treated with high-dose folinic acid (500 mg/m-2/week-1) plus 5-fluorouracil (400 mg/m-2/week-1 on day 1, and cisplatin (20 mg/m-2/week-1) 24 h after folinic acid infusion was completed. Out of 55 evaluable patients, 10 patients (18%) experienced a complete response with a mean duration of 11.4+ months, 25 patients had a partial response (45%) of 6.7+ months, 6 patients (11%) showed a stabilization of 4.8+ months, and 14 (25%) progressed. The overall response rate was 63.6% (95% confidence limits 56.5%-69.5%). Patients pretreated with radiotherapy had a 67% overall response rate, while those pretreated with chemotherapy showed a 54% overall response rate. All patients with cancer of the oropharynx had a major response, while patients with cancer of the oral cavity had the lowest response rate. The mean survival of patients who attained a complete response was 14.5+ months. Partial responders had a mean survival of 10.6+ months, while patients who progresses survived a mean of 3.6+ months. The treatment has been very well tolerated with few cases of grade 3 gastrointestinal toxicity. Grade 1-2 leukopenia was recorded in 64% of cases, grade 1-2 nausea/vomiting in 85%. In one case therapy was stopped because of persistent diarrhoea.
 ...
PMID:High-dose folinic acid and 5-fluorouracil plus cisplatin on a weekly schedule in the treatment of advanced cancer of the head and neck. 161 94

Thirty-six patients with advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with a regimen including cisplatinum (CP) 30 mg/m2 i.v., 5-fluorouracil (5-FU) 500 mg/m2 i.v. bolus, folinic acid (FA) 200 mg/m2 i.v. in a continuous one-hour infusion, and bleomycin (B) 15 mg i.m. on the first and second days and repeated every 28 days. Thirty-three patients (25 with recurrent disease and 8 untreated) are evaluable for objective response. Of these, 4 (12%) achieved CR and 15 (45%) PR. All of the untreated patients responded. The mean duration of response in the patients with recurrent or metastatic disease was 5.5 months (range 2-10+). Remission of symptoms, such as pain and dysphagia, was obtained in 58% and in 44%, respectively. Subjective remission occurred almost exclusively in objectively responsive patients. The major side effects were leukopenia (55%) and nausea/vomiting (58%). This regimen is active in the treatment of advanced SCCHN. The quality of life may be improved in responsive patients.
 ...
PMID:5-fluorouracil + folinic acid with cisplatinum and bleomycin in the treatment of advanced head and neck squamous cell carcinoma. 172 18

A significant increase in the dose intensity of chemotherapy with fluoropyrimidines and platinum complexes has resulted from selective circadian timing and/or circadian modulation of the infusion rate. The relevance of such chronopharmacologic strategy for improving the outcome of metastatic colorectal cancer was evaluated in an extended Phase II clinical trial involving 93 patients. Of these, 49% previously had received chemotherapy and/or radiation therapy. The drugs 5-fluorouracil (5-FU, 700 mg/m2/d) and folinic acid (FA, 300 mg/m2/d) combined with oxaliplatin (l-OHP, a nonnephrotoxic platinum complex, 25 mg/m2/d) were infused continuously for 5 days every 3 weeks. In a pilot randomized study, the infusion of all three drugs at a constant rate resulted in World Health Organization (WHO) Grade 3 or 4 toxicity in all four patients compared with no such toxicity in four patients if the infusion rate was modulated according to circadian rhythms. In this Phase II trial, drug delivery was modulated sinusoidally over the 24-hour day with peak flow rates at 4 AM for 5-FU and FA and at 4 PM for l-OHP, using an ambulatory programmable-in-time pump. All patients and 784 of 839 courses (93%) were evaluable for toxicity. Dose-limiting toxicities (WHO Grade 2 to 4) included diarrhea (19% of courses) and vomiting (35% of courses). In addition, WHO Grade 2 to 4 hematologic or mucosal toxicity, respectively, occurred in 2.5% and 7% of courses. Two toxic deaths were encountered. Peripheral sensory neuropathy led to discontinuation of l-OHP in 14 patients after 7 to 12 courses; it completely disappeared within 3 months. Fifty-four of the 93 patients had an objective response (58%; 95% confidence limits, 48% to 68%), irrespective of previous treatment or prior documented progression while receiving standard chemotherapy with 5-FU and FA or continuous 5-FU. Complete responses (CR) were seen in 6 patients (4 of which were proved histologically) and, after surgery, in 12 additional patients (overall CR rate, 18 of 93 [19%]; 95% confidence limits, 11% to 27%). Median progression-free survival (PFS) and overall survival were, respectively, 10 and 15 months, irrespective of prior therapy. Both PFS and survival were significantly longer in patients with a good performance status (PS, 0 or 1, by WHO criteria; respectively, 12 and 21 months) than in patients with poor PS (respectively, 8 and 10 months; P less than 0.01, by log-rank test). This chronopharmacologic protocol may have circumvented, to some extent, both the natural and acquired resistance of colorectal cancer to chemotherapy.
 ...
PMID:A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. 173 81

We report the results of a phase I study of intravenously administered cisplatin, 5-fluorouracil and high-dose folinic acid. This trial was designed to exploit potential biochemical interactions between these three agents. The maximum tolerated doses were cisplatin, 75 mg/m2, day 1; 5-fluorouracil, 375 mg/m2, days 1-5 and leucovorin 500 mg/m2, days 1-5. The dose-limiting toxic effect of this regimen was myelosuppression. Mild non-hematologic toxic effects were also observed and included nausea, vomiting, stomatitis, and diarrhea. Phase II trial of this regimen are underway, however randomized studies will eventually be necessary to establish whether cisplatin contributes clinically significant activity to this regimen.
 ...
PMID:Phase I clinical trial of cisplatin given i.v. with 5-fluorouracil and high-dose folinic acid. 235 61

Chemotherapy was given as initial therapy to 12 women with very advanced squamous cell carcinoma of the cervix and to 19 women with recurrent disease. They received a median of four courses of POMB which comprised vincristine 1.0 mg/m2 and methotrexate 300 mg/m2 followed by folinic acid rescue, bleomycin 30 mg as a 48-h infusion or intramuscular injection and cisplatin 100 mg/m2 as a 12-h infusion. Two of the 14 assessable patients with recurrent disease (14%) had a complete response with no disease found histologically in one, and seven (50%) had a partial response. Although the actuarial median survival of all 19 patients with recurrent disease was 8 months, five patients have remained free from tumour progression for a median of 17 months from start of chemotherapy. Six of the 10 assessable patients receiving initial chemotherapy (60%) had a complete response (confirmed histologically in two) and two (20%) had a partial response. Nine patients had additional treatment with radiotherapy and or surgery. Although only four of the patients remain disease-free at 61, 51, 7 and 4 months, all but two were initially FIGO stage IV. Although cisplatin-induced emesis is controllable and the side-effects of methotrexate can be avoided, the POMB regimen remains potentially toxic. The small number of patients with very advanced disease who are long-term survivors prompts us to study further the role of aggressive chemotherapy as the initial treatment of patients with visceral or nodal involvement from carcinoma of the cervix.
 ...
PMID:Cisplatin, vincristine, methotrexate and bleomycin (POMB) as initial or palliative chemotherapy for carcinoma of the cervix. 244 33


1 2 3 4 5 6 7 Next >>