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)

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 multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.
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PMID:[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group]. 983 8

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

Multidrug resistance is a major obstacle in successful systemic therapy of gynecologic malignancies. The objectives of this study are to evaluate the activity of cyclosporin A used to overcome drug resistance in a variety of gynecologic malignancies. Forty women (29 with ovarian cancer, 7 with uterine cancer, 3 with cervical cancer, and 1 with choriocarcinoma) were treated with cyclosporin A, 4 mg/kg intravenously, 6 hours before and 18 hours after the specific chemotherapeutic agent, to which the tumor had developed drug resistance. All patients had shown resistance to the chemotherapy agent used in combination with cyclosporin A. All patients had been heavily pretreated (mean, 2.8 previous chemotherapy regimens). Overall, among 38 available patients with gynecologic malignancies, a 29% objective response rate was observed. Twenty-six (65%) of all patients received three or more cycles of cyclosporin A. There was a 25% response rate for patients with ovarian cancer patients and 50% for those with uterine cancer. There were no responses among the three patients with cervical cancer, and the patient with choriocarcinoma had a complete response. All patients were evaluable for toxicity. Leukopenia and nausea were the most common toxic reactions, but in most cases they were transient, and only three patients required a treatment delay. The most common grade 3 or 4 toxicity was thrombocytopenia, which was observed in 22% of the patients. Cyclosporin A is well tolerated and has significant potential for reversal of chemoresistance in heavily pretreated patients with ovarian and uterine malignancies.
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PMID:Cyclosporin A reverses chemoresistance in patients with gynecologic malignancies. 1093 45

The aim of this study was to evaluate the survival of 395 previously untreated cervical cancer patients with at least one high risk factor following concurrent chemoradiation and to assess the toxicities. Two different chemotherapy regimens were used for concurrent chemoradiation. In the patients with squamous cell carcinoma, 100 mg/m2 of cisplatin was infused intravenously, followed immediately by five consecutive daily administrations of 5-fluorouracil, 1,000 mg/m2/day, each infused intravenously over 24 hr. As for the patients with adenocarcinoma, 70 mg/m2 of cisplatin, 250 mg/m2 of cytoxan and 45 mg/m2 of adriamycin were administered intravenously on days 1, 2, and 3, respectively. The 5-year survival rate was 54.4% with stage III and IV, 62.6% with lymph node metastasis on computed tomogram or MRI, 77.9% with stage I-II disease with lesion size > or =4 cm, and 50.3% with small cell carcinoma or adenocarcinoma. Side effects from concurrent chemoradiation such as nausea, vomiting, and alopecia were present in all 395 cases. Anemia, leukopenia, thrombocytopenia, hepatotoxicity, and nephrotoxicity were observed to varying degrees, but there was no toxic death. This study suggests that cisplatin-based concurrent chemoradiation in treating cervical cancer patients with high risk factors is effective and relatively well tolerated, with acceptable toxicity.
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PMID:Concurrent chemotherapy and radiotherapy in invasive cervical cancer patients with high risk factors. 1098 93

Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I-II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 microg) was given on days 3-12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m(-2)). A total of 27 patients (stage IV=seven, recurrence=20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m(-2), respectively, and the recommended doses were 50 and 80 mg m(-2). Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 non-haematologic toxicities except for nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39-78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61-711 days) and 415 days (range: 74-801 days). This new regimen is promising for cervical cancer.
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PMID:Phase I-II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer. 1529 35


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