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)

Nedaplatin is a derivative of cisplatin which produced less nausea & vomiting and nephrotoxicity. In the phase I study, the MTD was 120 mg/m2 and the DLF was a bone marrow suppression. The optimal dose in a phase II study was judged to be 100 mg/m2 repeated every 4 weeks. In the phase II studies, response rates obtained were 42.2% for head & neck ca., 40.9% for small cell lung ca. (SCLC), 20.5% for non-SCLS (NSCLC), 12.5% for breast ca., 51.7% for esophageal ca., 8.3% for stomach cancer. 0 for colon ca., 38.1% for bladder ca., 14.3% for pyelo-ureter tract ca., 18.8% for prostatic ca., 80.0% for testicular tumor, 37.3% for ovarian ca., 46.3% for cervical ca. Grade 3.4 thrombocytopenia, leukopenia, anemia and nausea & vomiting were found in 28.5%, 21.1%, 16.8% and 18.5% respectively. In an additional phase II study for cervical ca. at a dose reduced to 80 mg/m2, a response rate was comparable together with less thrombocytopenia. In a randomized controlled study of nedaplatin plus vindesine vs. cisplatin plus vindesine in NSCLC, there was no significant difference in response, however mephro and G.I. toxicity were significantly less in the nedaplatin group. Thrombocytopenia was found more frequently in the nedaplatin groups. Based on the results, the indication was approved in ca. of the head & neck, SCLC, NSCLC, esophagus, bladder, testicular tumor, ovary and cervix. Dose schedule is 80 - 100 mg/m2 every 4 weeks at more 1,000 mL drip infusion repeated.
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PMID:[Nedaplatin]. 871 35

Persistent or recurrent squamous malignancies of the female genital tract are usually incurable by conventional therapy, and results of single agent chemotherapy have been disappointing. We undertook this study to confirm a previously reported response rate of 69%, using a regimen of bleomycin 30U, ifosfamide 5g/m2 with mesna 6g/m2, and cisplatin 50 mg/m2 (BIP) for recurrent cervical cancer. This regimen was used to treat persistent or recurrent squamous cancers in women with cervical cancer (n = 11), vaginal cancer (n = 1) and vulvar cancer (n = 1). Results were reviewed retrospectively and toxicities graded according to the criteria of the Gynecologic Oncology Group. No complete responses were seen. One patient had a partial response (10%, 95% confidence interval 0-28%). Five patients (50%), exhibiting stable disease during therapy with BIP, progressed after cessation of therapy. Of 9 women with symptoms after one cycle. Significant toxicities included neutropenic fever (3 grade 3, 3 grade 4), emesis (1 grade 3), confusion (2 grade 4), vaginal bleeding (2 grade 3), and renal failure (1 grade 3). Eight patients were transfused with a total of 28 units of red cells. After 23 months of follow-up, all patients were dead of disease. Mean survival was 10 months. Toxicity associated with this regimen can be significant, and results appear no better than those reported with single agent therapy.
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PMID:A bleomycin/ifosfamide/cisplatin regimen exhibits poor activity against persistent or recurrent squamous gynecologic cancers. 875 May 8

An early phase II cooperative study of Gemcitabine Hydrochloride (abbreviated to "gemcitabine" herewith) was conducted in patients with a variety of solid tumors (i.e., lung cancer, gastric cancer, pancreatic cancer, colon/rectum cancer, cervical cancer, ovarian cancer and breast cancer) at 56 institutions. The aim of the first step (Step I) was to investigate the feasibility of gemcitabine in a variety of different solid tumors, including lung cancer regarding efficacy and safety. The aim of the second step (Step II) was as a result of step I (Responses were observed) to continue to investigate the efficacy and safety of gemcitabine in chemonaive patients with non-small cell lung cancer. As a Step I study, gemcitabine was administered once weekly at a dose of 800 mg/m2 for a consecutive 3-week period followed by a week of rest, in multiple courses. Among the 29 eligible patients with lung cancer, partial response (PR) was achieved in 3 patients (25.0%, 95% confidence interval: 5.5-57.2%) out of 12 chemonaive patients. Adverse reactions (grade 3 or higher) seen in 29 patients with lung cancer were neutropenia (27.6%), leukopenia (13.8%), decreased hemoglobin (13.8%), thrombocytopenia (10.3%), malaise (6.9%), anorexia (3.4%), nausea/vomiting (3.4%), diarrhea (3.4%), dyspnea (3.4%) and interstitial pneumonia (3.4%). In other types of solid tumors, PR was achieved in 2 (8.7%) out of 23 eligible patients with cervical cancer and in 1 (5.3%) of 19 eligible patients with ovarian cancer, while the use of analgesics became unnecessary in 1 patient with pancreatic cancer. Incidence as well as severity of main adverse reactions in these patients were comparable to those seen in patients with lung cancer. A Step II study, in which gemcitabine was administered once weekly at a dose of 1,000 mg/m2 to chemonaive patients with non-small cell lung cancer, was conducted, referring to the results of Step I and clinical studies conducted overseas. The results of the Step II study demonstrated PR in 5 (14.3%, 95% confidence interval: 4.8 - 30.3%) out of 35 eligible patients with non-small cell lung cancer and that the main adverse reactions were comparable to those seen in the Step I study, posing no tolerability problems in particular.
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PMID:[An early phase II study of gemcitabine hydrochloride (LY 188011). Gemcitabine Cooperative Study Group for Early Phase II]. 893 92

To assess the efficacy and the compliance of weekly cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer, 23 patients, FIGO stage IB-IIA > 4 cm-IIB, were recruited. Treatment consisted of four weekly courses of cisplatin (1.5 mg/kg): 91% of the patients received the planned therapy without dose reduction or delay. Toxicity was mild: delayed emesis was the most common side effect. Overall clinical response rate was 85% with a complete response in 28%. Nineteen patients underwent surgery without any undue increase in morbidity. Histologic analysis of surgical specimens revealed a complete response in 25% of stage IB-IIA patients; in only one case of stage IIB, was residual parametrial involvement present. In conclusion, weekly cisplatin is highly effective, with lower cost and less toxicity compared to other neoadjuvant chemotherapy regimens.
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PMID:Weekly cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer: a well-tolerated alternative. 917 29

An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide. One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle. Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy. In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise. The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).
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PMID:[TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies]. 927 44

The aim was to perform a broad phase II and pharmacokinetic study of methoxymorpholino-doxorubicin (MMRDX), a drug active against multidrug-resistant tumour cells in vitro when given by i.v. bolus at 1.5 mg m(-2) every 4 weeks, in metastatic or unresectable solid tumour patients with known intrinsic drug resistance. Patients received a maximum of six cycles. Plasma, urine and leucocyte MMRDX and its 13-dihydro metabolite pharmacokinetic analysis was performed in patients without liver metastases. Patients (n = 48, 21 NSCLC, 19 renal cell, three head and neck tumour, three cervical cancer and two adenocarcinoma of unknown primary) received 132 cycles of MMRDX. Common toxicity criteria (CTC) grade III/IV thrombocytopenia (12% of cycles) and neutropenia (27% of cycles) occurred with median nadir on day 22. Transient transaminases elevation > grade III/IV was observed in 7% of cycles, late and prolonged nausea > or = grade II in 34% and vomiting > or = grade II in 39%. In two patients, the left ventricular ejection fraction was reduced > or = 15%. Of 37 evaluable patients, one out of 17 NSCLC had a partial response. Mean (+/- s.d.) MMRDX AUC0-infinity calculated up to 24 h after dosing was 20.4 +/- 6.2 microg h l(-1) (n = 11) and t(1/2, gamma) was 44.2 h. Mean plasma clearance (+/- s.d.) was 37.2 +/- 7.3 l h(-1) m(-2) and volume of distribution 1982 +/- 64 l m(-2). MMRDX leucocyte levels 2 and 24 h after infusion were 450 to 600-fold higher than corresponding MMRDX plasma levels. In urine, 2% of the MMRDX dose was excreted unchanged, and 2% as metabolite. The main side-effects of 1.5 mg m(-2) every 4 weeks of MMRDX are delayed nausea and vomiting and haematological toxicity. MMRDX is characterized by extensive clearance and rapid and extensive distribution into tissues. A low response rate was observed in patients with tumours with intrinsic chemotherapy resistance.
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PMID:Broad phase II and pharmacokinetic study of methoxy-morpholino doxorubicin (FCE 23762-MMRDX) in non-small-cell lung cancer, renal cancer and other solid tumour patients. 945 59

We conducted a multi-site late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer in cooperation with 32 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Treatment cycles were to be repeated at 4- to 5-week intervals. Eighty patients were enrolled and 70 patients were evaluated. The overall response rate (95% CI), including one complete response patient and 18 partial response patients, was 27.1% (19/70). The most commonly observed toxicity was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were gastrointestinal toxicities such as anorexia, nausea, stomatitis and vomiting, as well as fatigue and alopecia. These adverse effects were well tolerated and controlled with medications. From these results we concluded oral etoposide administered for 21 consecutive days was an effective drug against cervical cancer.
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PMID:[Late phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical cancer. ETP 21 Study Group--Cervical Cancer Group]. 988 Oct 82

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

Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m(2)) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m(2) i.v.) on day 1 over 90 min. The patients' median age was 57 years (range 35-75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41-74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16-62 days). The median survival was 27. 7+ months (range, 6.4-52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.
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PMID:Phase II study of irinotecan and cisplatin as first-line chemotherapy in advanced or recurrent cervical cancer. 1064 38

Multiple metachronous primary malignancies are becoming increasingly frequent; however, multiple synchronous primary malignancies are still unusual. We report the case of a 61-year-old woman with synchronous stage IIIB ductal carcinoma of the left breast and FIGO stage IB2 squamous cell carcinoma of the cervix. The patient was treated initially every 4 weeks with a 24-h intravenous infusion of paclitaxel (175 mg/m2) followed by a 1-h infusion of carboplatin (area under the curve of 5 mg/ml x min) with concurrent irradiation of the pelvis. Significant toxic reactions including nausea, vomiting, and diarrhea required hospitalization or outpatient intravenous fluids and antiemetics. After four cycles of chemotherapy, the breast cancer was in complete clinical remission, and the patient underwent a modified radical mastectomy with axillary lymph node dissection. Pathologic findings revealed a few microscopic foci of residual infiltrating ductal carcinoma exhibiting a marked treatment effect; none of the 14 axillary lymph nodes removed showed evidence of metastatic tumor. A near-complete pathologic response of the breast cancer and a complete clinical response of the cervical cancer were obtained. Adjuvant chemotherapy for the breast cancer was then initiated, followed by radiation and hormonal therapy.
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PMID:Synchronous primary cancers of the breast and cervix: planning multidisciplinary primary treatment [clinico-pathological conference]. 1068 89


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