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)

Recently, granisetron (KYT), one of the 5-HT3 receptor antagonists, has been developed and proved to have a strong effect for cisplatin (CDDP)-induced emesis. The combination chemotherapy with CDDP and 5-fluorouracil (5-FU), which has great efficacy for head and neck cancer, induces nausea and vomiting as side effects. We compared the effects of KYT for CDDP plus 5-FU-induced emesis between two administration schedules. Forty patients were randomized to two groups. KYT was administered either on day 1 for twenty patients (Group A), or for consecutive 5 days in another twenty patients (Group B). Additional antiemetics were administered in thirteen patients in Group A and seven patients in Group B for severe nausea and vomiting even after KYT administration. The times of additional antiemetics administration were more frequent in Group B. The nausea score was statistically lower in Group B and the duration of nausea or vomiting was statistically longer in Group A. The frequency of vomiting was the same in the two groups on day 1, but it was controlled faster in Group B. Appetite loss was lower on day 7 in Group B. It was concluded that vomit and nausea were controlled better in Group B after day 4. Additional antiemetics were not effective, and 5 consecutive administrations of KYT for chemotherapy with CDDP plus 5-FU was effective for late emesis.
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PMID:[Comparison of effects between single vs five-day injection of granisetron for combination chemotherapy with cisplatin and 5-fluorouracil for head and neck cancer]. 923 62

We performed a phase II study to evaluate the activity and toxicity of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin as first-line treatment in patients with recurrent or metastatic head and neck cancer. From March 1994 until August 1996, 49 patients were treated with paclitaxel 200 mg/m2 by 3-hour infusion followed by carboplatin at an area under the concentration-time curve of 7 mg/mL x min; treatment was requested every 4 weeks. Granulocyte colony-stimulating factor was administered prophylactically on days 2 to 12 of each cycle. The study included 41 men and eight women, with a median age of 57 years (range, 23 to 73 years). Most of the patients were symptomatic and had locoregional disease. Primary sites included nasopharynx (14 patients), oropharynx (six), oral cavity (four), hypopharynx (three), larynx (20), paranasal sinuses (one), and unknown (one). After the completion of treatment, four patients (8%; 95% confidence interval, 0% to 16%) achieved a complete response and 12 (24%; 95% confidence interval, 12% to 37%) achieved a partial response. Grade 3/4 toxicities included anemia (2%) and leukopenia, thrombocytopenia, nausea/vomiting, diarrhea, and stomatitis (4% each). After a median follow-up of 15.3 months, median time to progression was 5.7 months (range, 0.5 to 29.8+ months) and median survival was 13.3 months (range, 0.5 to 30.2+ months). In our ongoing study in a similar patient population, gemcitabine was substituted for carboplatin.
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PMID:Paclitaxel in combination with carboplatin or gemcitabine for the treatment of advanced head and neck cancer. 942 62

A phase III, single-institution, open, prospective, randomized, parallel study was carried out on head and neck cancer patients to compare a combination of low-dose (20 mg q.i.d.) oral metoclopramide (M) + i.m. Dexamethasone (D) with an oral 5-HT3-Receptor Antagonist (5-HT3-RA) alone in the prevention of high-dose (HD > or = 80 mg/m2) cisplatin-induced delayed emesis. 51 consecutive patients, all but two with advanced stage of disease, were treated for a total of 198 chemotherapic cycles: 23 patients entered Group A (5-HT3-RA) receiving a total of 108 cycles, 28 patients entered Group B (M + D) receiving a total of 90 cycles. The treatment groups were well matched for age, sex (almost all patients were males), ECOG PSR, stage of disease and alcohol intake. The efficacy of M + D was significantly higher than that of 5-HT3-RA in achieving complete protection (CR 88.9% vs 72.2%, chi2 9.9, p = 0.002) and major efficacy (ME: CR + MR) (94.5% vs 85.2%, chi2 5.6, p = 0.02). Generally, for both treatments (5-HT3-RA and M + D) a good control of delayed emesis was achieved in patients who had complete protection on acute emesis. A good control of acute emesis had a highly positive predictive value of delayed emesis for both treatments without significant difference between them (CR 85% for M + D and 82% for 5-HT3-RA; ME 88% for M + D and 92% for 5-HT3-RA). The failure (F) on acute emesis had a significantly higher negative predictive value of delayed emesis for M + D (98%) than 5-HT3-RA (67%). Our study is, to our knowledge, the first comparing M + D vs one 5-HT3-RA alone in the prevention of HD cisplatin-induced delayed emesis in a properly designed clinical trial. Our results show that M + D are more effective than 5-HT3-RA alone in the prevention of HD cisplatin induced delayed emesis, whereas 5-HT3-RA may be the treatment of choice in patients who had acute vomiting. Our study demonstrated not only the persistence of antiemetic efficacy but also increasing efficacy, during subsequent courses. Our results confirm that protection from acute emesis plays a major role in the appearance and control of delayed emesis.
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PMID:Comparison of oral 5-HT3-receptor antagonists and low-dose oral metoclopramide plus i.m. dexamethasone for the prevention of delayed emesis in head and neck cancer patients receiving high-dose cisplatin. 945 81

Some clinical parameters play a role in developing effective antiemetic therapy. In the present study, 310 patients entered and 301 were evaluable. They received cisplatin based combination chemotherapy (100 mg/m2), with antiemetic therapy based in metoclopramide, at a standard dose and schedule (2 mg/kg in 5 doses). Patient characteristics such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss >15%, previous chemotherapy, previous radiotherapy, history of vomiting during pregnancy, additional drugs (dexamethasone, alprazolam), in the antiemetic regimen were included in the evaluation. We also studied the manifestation of anxiety and depression and the presence of psychosocial problems related to therapy, evaluated them with specific psychological indexes modified for our study. We evaluated incidence of vomiting, retches, and nausea, with several scales. We distinguished three groups of factors influencing nausea and vomiting. Factors that predicted for increased nausea and vomiting was gender (women), stress and age (younger patients experienced more prolonged duration and higher grades of nausea). The addition of alprazolam (a sedative drug) and dexamethasone, was associated with decreased incidence of nausea and vomiting. The weight loss (increased nausea and decreased vomiting control according to Gralla's scale). Previous chemotherapy decreased the number of patients without nausea and vomiting control according to Gralla's scale. Patients with previous radiotherapy presented an increased grade of nausea. Patients with head and neck cancer presented less nausea with shorter duration, less frequent episodes of vomiting. Patients with ovarian cancer presented increased mean number of retches. In conclusion, despite difficulties in assessing nausea and vomiting among clinical trials, several factors, especially stress, gender, weight loss, additional drugs (corticosteroids and sedatives) may play an important role in modulating the antiemetic response.
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PMID:Factors that influence the antiemetic activity of metoclopramide to cisplatin based chemotherapy. 968 26

This review summarizes the results reported in preclinical and clinical trials of three novel anticancer drugs developed and tested in Japan. In phase II trials, Irinotecan, a semisynthetic analog of camptothecin, has yielded response rates exceeding 20% in non-small-cell lung cancer, small-cell lung cancer, breast cancer, gastric cancer, colorectal cancer, ovarian cancer, uterine cervical cancer, and non-Hodgkini's lymphoma. It was modestly active on pancreatic cancer and was not active on acute leukemias. Dose-limiting toxicities were leukopenia and diarrhea, and other major toxicities were nausea, vomiting, and alopecia. Amrubicin, a totally synthetic anthracycline, exhibited both higher efficacy on human tumor xenografts and cardiotoxicity milder than that of doxorubicin in preclinical studies. The dose-limiting toxicity in phase I trials was leukopenia. In phase II trials, amrubicin has shown activity equivalent to that of doxorubicin on non-Hodgkin's lymphoma, response rates exceeding 20% on non-small-cell lung cancer, and a response rate of 78.8% on untreated extensive-stage small-cell lung cancer. S-1 is an oral formulation consisting of ftorafur (an analog of 5-fluorouracil), 5-chloro-2, 4-dehydropyrimidine, which inhibits degradation of 5-fluorouracil, and potassium oxonate, which reduces gastrointestinal toxicity, at a molar ratio of 1:0.4:1. In phase I trials, dose-limiting toxicities (myelosuppression and gastrointestinal toxicities) were judged to be milder than those induced by UFT (ftorafur plus uracil). The response rates obtained in phase II trials were 40-49% on advanced gastric cancer, 35.5% on colorectal cancer, 37.5% on head and neck cancer, and 40.7% on breast cancer.
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PMID:Novel anticancer drugs in Japan. 1023 66

Forty-two patients with advanced head and neck cancer entered this phase II trial of long-term continuous 5-fluorouracil (5-FU) infusion at a dose of 300 mg/m2/day for a maximum of 16 weeks. Objective response rate was 15% in 41 evaluable patients. Median time to progression was 2.9 months, and median survival 4 months. Toxicity was generally mild. Reversible stomatic and hand-foot syndrome WHO grade III-IV was observed in 5 and 3 patients, respectively. Haematologic toxicity and emesis were less pronounced with no grade III-IV toxicity. One patient had to discontinue treatment because of ataxia. No catheter-related toxicity and no treatment-related mortality were observed. In the present study long-term continuous infusion of 5-FU has only modest activity in terms of response rate, but the activity is comparable with other single-agent regimens. The treatment is well tolerated, with minimal toxicity making it usable in a palliative situation.
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PMID:Long-term continuous 5-fluorouracil infusion in patients with advanced head and neck cancer. 1066 60

Gemcitabine (2',2'-difluorodeoxycytidine) is a nucleoside analog with antitumor activity against a variety of malignancies. The critical enzyme cytidine kinase is saturated at plasma concentrations achieved after a 30-min infusion at conventional doses. Prolonged infusion time may yield higher intracellular dFdCTP concentrations. A phase I study was designed to determine the maximum tolerated dose (MTD) of gemcitabine, given by infusion for 3 h, in heavily pretreated patients. Twenty-seven patients (13 head and neck cancer, seven sarcoma, three esophageal cancer, three non-small-cell lung cancer and one ovarian cancer) were enrolled. Twenty patients were defined as refractory at first- or second-line chemotherapy. Four different entry dose levels (300, 400, 450 and 500 mg/m(2)) were evaluated for gemcitabine administered on days 1, 8 and 15 of a 28-day cycle. The MTD was defined as 450 mg/m(2), with granulocytopenia, thrombocytopenia and asthenia being dose limiting. The maximum grade III/IV patient toxicities for hemoglobin, leukocytes, neutrophils and platelets for all doses were 7, 19, 19 and 11%, respectively. Non-hematological toxicities included asthenia, nausea/vomiting and diarrhea. Thus, gemcitabine administered at a fixed 3-h infusion was well tolerated up to 450 mg/m(2) in heavily pretreated patients. Myelosupression and asthenia were dose-limiting toxicities.
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PMID:Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily pretreated advanced solid tumors. 1159 51

A late phase II clinical study of S-1, a novel oral antitumor agent of fluorinated pyrimidines, in patients with advanced/recurrent head and neck cancer was conducted in 25 institutions across Japan as a multi-institutional cooperative study from August 1995 to March 1998. Out of 59 eligible patients, the objective responses were 4 complete responses (CR) and 13 partial responses (PR). The response rate was 28.8% (17/59, 95% CI: 17.8-42.1%). The response rate in previously treated patients was 28.3% (15/53), whereas that in treatment naive patients was 33.3% (2/6). The response rate in patients with prior chemotherapy was 26.7% (12/45). Major adverse reactions of grade 2 or more were anemia (25.4%, 15/59), leucopenia (22.0%, 13/59), neutropenia (25.4%, 15/59), thrombocytopenia (3.4%, 2/59), anorexia (6.8%, 4/59), nausea/vomiting (1.7%, 1/59), stomatitis (1.7%, 1/59), skin symptoms including eruptions or desquamation (5.1%, 3/59), and malaise (1.7%, 1/59). Grade 4 anemia was observed in one case; however, this returned to the normal level after the termination of drug administration and the blood transfusion. Therefore, this event was confirmed to be reversible. Based on these results, we conclude that S-1 is an active agent for the treatment of advanced/recurrent head and neck cancer.
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PMID:[Late phase II study of S-1 in patients with advanced head and neck cancer]. 1168 Dec 45

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m2 was weekly given by short infusion, and nolatrexed 725 mg/m2 per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA. 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.
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PMID:Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer. 1182 60

Very few large multi-institutional comparative clinical studies for head and neck cancer are reported in Japan. Many studies for organ-preservation with better QOL have been reported around the world, and comparative clinical studies are also necessary in Japan to evaluate organ-preservation treatment. I reviewed comparative clinical studies for head and neck cancer in Japan. Inuyama et al. reported a multi-institutional randomized clinical trial (RCT) that compared the efficacy of CBDCA + PEP and CDDP + PEP. Comparative clinical studies for combination chemotherapy, CDDP + PEP + MTX (PPM) vs. CDDP + PEP + 5-FU (PPF), and PPM vs. CDDP + PEP (PP) are reported. Effects and toxicity are different with each regimen, but the differences are not statistically significant. An RCT of neoadjuvant chemotherapy (NAC) for nasopharyngeal cancer with a small sample size was reported. Three-year survival was significantly better for the NAC group. An RCT of concurrent chemo-radiotherapy with CDDP vs. CBDCA was also reported. CBDCA with radiation was significantly better in terms of 2- and 5-year survival. This result is interesting but the low-dose CDDP with radiation 4 times per week is not standard. A large nationwide RCT with 560 cases investigating adjuvant chemotherapy with UFT was conducted in 1987. The differences in 3-year survival and 3-year disease-free survival with or without UFT adjuvant were not statistically significant, but the incidence of distant metastasis was significantly lower in the UFT adjuvant group. Comparative clinical studies of 5-HT3 antagonists for chemotherapy including CDDP are reported. We conducted a crossover comparative clinical study on the combination of azasetron and dexamethasone. The combination with dexamethasone significantly prevented acute emesis induced by CDDP. Comparative clinical studies of head and neck cancer have not provided good evidence, with the exception of an RCT of adjuvant chemotherapy with UFT, in the past. Well-designed comparative clinical studies with the cooperation of head and neck surgeons, radio-oncologists, and medical oncologists should be considered in order to acquire high-level evidence.
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PMID:[Comparative clinical studies for head and neck cancer in Japan]. 1235 35


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