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)

A combination of doxorubicin ('Adriamycin") and B.C.N.U. (1,3 di[2-chloroethyl]-1-nitrosourea) (30 mg/m2 of each intravenously every 3-4 weeks) was used to treat thirteen multiple-myeloma patients who did not respond or were in relapse after remission produced by alkylating-agent/prednisone therapy. All cases were staged according to total-body myeloma-cell number and followed quantitatively for response to therapy. Seven of the thirteen patients responded (54%). Two had complete clinical remissions and a greater than 75% reduction in tumour-cell mass lasting 12 and 16 months. Five others had partial remissions with lesser degrees of tumour-mass reduction and bone pain and improved haemoglobin and serum-albumin concentrations. Toxicity was limited to occasional myelo-suppression, mild alopecia, and nausea. The results indicate the usefulness of doxorubicin/B.C.N.U. for myeloma patients who have relapsed during previously effective alkylating-agent therapy.
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PMID:Doxorubicin/B.C.N.U. chemotherapy for multiple myeloma in relapse. 5 35

The recent successes being achieved with combination chemotherapy regimens strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remission (CRs). The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease free. The expected survival of patients with unresectable LAD is approximately 4-6 months without any treatment and 6-9 months with standard chemotherapy. Compared with the latter results, the preoperative use of etoposide, adriamycin, and platinum (EAP) seems to improve the prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stage IIIa or IIIb). However, partly because of the severe toxicities (myelo-suppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens. Considering the predominantly palliative treatment intentions in far-advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53%, including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. The high remission rate and long medical survival time achieved with ELF, plus its good tolerability, make this combination a valuable alternative to anthracycline-containing regimens. In addition to developing new treatment plans and strategies, it is also desirable to predict treatment outcome with an acceptable degree of certainty. Combinations of variable defined patient subgroups with significantly different probabilities for achieving objective response and for survival. The results of this analysis may contribute to a more patient-oriented and risk-adapted chemotherapy and to better comparability of future studies.
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PMID:New developments in the treatment of gastric carcinoma. 168 67

Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside (Ara-C), was conducted by cooperative study groups between January 1986 and June 1987. The dosage for the single and 5-day oral administration ranged 50 to 1,200 and 100 to 900 mg/body/day, respectively. The main adverse effects were myelo-suppression and gastrointestinal toxicities such as nausea, vomiting, anorexia and diarrhea. In the single administration, the maximum tolerated dose (MTD) could not be determined, however, in the 5-day schedule MTD was considered to be 700 to 900 mg/body/day, and the dose limiting factor to be thrombocytopenia. After the single administration (800 mg/body/day) of YNK01, the plasma concentration of Ara-C, an active metabolite of YNK01, was 3.43 ng/ml (Cmax) at 24 hrs. and 0.82 ng/ml at 72 hrs. During the 5-day administration for 300 mg/body/day and 500 mg/body/day, the Ara-C concentration changed from 2.3 to 4.1 ng/ml, and from 1.5 to 11.9 ng/ml respectively, and sustained almost the same concentration as to during the administration period until the 2nd day after the completion of the administration.
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PMID:[Phase I study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate)]. 224 Nov 85

Four patients with recurrent or advanced endometrial cancer have undergone combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP). All drugs were administered by I.V. on day 1 in the following doses: Cyclophosphamide 500 mg/m2, Adriamycin 50 mg/m2 and Cisplatin 50 mg/m2. The treatment was repeated every 4 weeks and continued as long as there was disease progression. Two complete clinical responses and two partial responses were achieved. Based on these good results, we have initiated post-operative prophylactic chemotherapy using CAP in high risk patients. Adverse effects including myelo-suppression, nausea, and vomiting, and alopecia were seen in almost all patients. In no case, however, did any patient experience life-threatening toxicity. Based on our experience, CAP therapy appears tolerable when used per our schedule.
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PMID:[Combination chemotherapy using cyclophosphamide, adriamycin, and cisplatin in recurrent or advanced endometrial cancer--a preliminary report]. 292 85

Ethylenediamine platinum(II) malonate [JM-40 (NSC 146 068)] has been selected for clinical studies because of its favorable preclinical toxicity profile as a "second generation" platinum analogue. When compared to cisplatin, JM-40 was less emetic in the ferret and less nephrotoxic in the dog, while its antitumor activity approached that of cisplatin. Twenty-nine patients received 86 courses of JM-40 as a single dose every 3-4 wk. After 13 dose escalation steps the maximum tolerable dose was reached at 1200 mg/m2. The dose limiting toxicities were nausea, vomiting, and nephrotoxicity. The renal damage seemed reversible up to a dose level of 1000 mg/m2 and consisted of a glomerular and tubular dysfunction. JM-40 did not cause any other dose related side effect or myelo-suppression. Pharmacokinetic studies at a dose of 1000 mg/m2 revealed mean terminal half-lives of 5.0 and 1.9 days for platinum in plasma and plasma ultrafiltrate, respectively. The mean cumulative excretion of platinum in urine accounted for 57% of the dose up to day 5. Two partial responses were observed in a patient with a large cell carcinoma of the lung and in one with a carcinoma of the lacrimal gland. Limited evaluation of JM-40 in phase II studies is warranted. The recommended dose is 1000 mg/m2 every 4 wk and 800 mg/m2 for patients pretreated with platinum analogues.
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PMID:Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue. 394 86

Fourteen patients with advanced ovarian carcinoma previously treated with chemotherapeutic agents including cisplatin were treated with vinblastine 0.1 mg/kg intravenously every week. There were no responses in 13 evaluable patients. The median survival was 19+ weeks following the initiation of vinblastine (VBL) therapy. Toxicity consisted of minimal myelo-suppression (WBC count less than 2500/microliter in 8/78 courses, WBC count less than 1500/microliter in 0/78 courses, platelets less than 150,000/microliter in 0/78 courses), nausea (4/13 patients), vomiting (2/13 patients), neuropathy (4/13 patients), and weakness and fatigue (6/13 and 5/13 patients, respectively). Although data derived from the human tumor stem cell assay (HTSCA) suggest that VBL may be an active agent against previously treated ovarian carcinoma, this study in patients with refractory advanced disease suggests that VBL is inactive (less than 20% response rate with 90% confidence levels) in that setting. Whether significant durable benefit can be achieved with VBL therapy in patients whose tumor is sensitive in the HTSCA remains to be seen.
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PMID:Phase II study of vinblastine in advanced refractory ovarian carcinoma. 661 22

A study of the feasibility of gradually increased epirubicin and cyclophosphamide dosage in an FEC regimen with G-CSF (granulocyte colony stimulating factor) support in 18 high-risk breast cancer patients as adjuvant treatment was carried out. The FEC regimen was initiated with 5-fluorouracil 600 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 900 mg/m2 together with G-CSF 5 micrograms/kg subcutaneously on days 2-15 q 3 weeks for nine cycles, increasing individually through four dose levels to a maximum of 5-FU 600 mg/m2 (not escalated), epirubicin 120 mg/m2 and cyclophosphamide 1800 mg/m2. Transient cytopenias were regularly observed without major clinical complications. Rapid recovery and a biphasic overshoot of granulocytes required individualization of G-CSF support. During the 6-month treatment period, a general decline in granulocytes, platelets and haemoglobin was observed, resulting in maximal dose intensity in the middle of the treatment period. Compared to a conventional FEC regimen (5-Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2, Cyclophosphamide 600 mg/m2 q 3 w) without dose reductions, it was feasible to increase the dose of epirubicin by more than 50 per cent with an increased dose intensity between 25 and 70 per cent. The dose of cyclophosphamide was increased by more than 100 per cent. All patients suffered from complete alopecia and moderate nausea, but there was no acute cardiac or severe mucosal toxicity. It was concluded that intensified, G-CSF supported FEC therapy can be safely administered in an outpatient setting, provided the patients are thoroughly informed and adequately monitored. High-risk patients are enrolled in a study comparing the described regimen and a myeloablative regimen including peripheral stem-cell support. Breast cancer seems to respond to chemotherapy in a dose dependent manner, suggesting the use of dose intensified regimens (1,8,9,11). This approach is currently under investigation in studies comparing standard regimens with myelo-ablative regimens in high-risk primary breast cancer (3,10). In a Scandinavian multicenter study (2), two high dose regimens, G-CSF supported dose-escalated FEC and myeloablative cyclophosphamide-thiotepacarboplatin with peripheral stem cell support, are compared as adjuvant therapy in operable high-risk breast cancer. This phase I study was performed to assess the feasibility and achievable dose intensity of an individually dose-escalated FEC regimen not in previous use.
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PMID:Acute hematologic feasibility of G-CSF supported dose-escalated FEC therapy as adjuvant treatment after breast cancer surgery. 1065 Jul 87

Advanced thoracic esophageal cancer has a poor prognosis despite advances in surgery, such as three-field lymph node dissection. Multimodal therapy is needed to improve local control, resectability and survival rate. Fifteen patients with advanced squamous cell carcinoma of the thoracic esophagus were treated with neoadjuvant chemoradiotherapy (NAC) combined with concurrent radiation (30 Gy/12 f) and 3 courses of 5-FU and CDDP (CDDP 5 mg/m2/day + 5-FU 250 mg/m2/day: day 1-5: div). In the absence of unresectable disease and surgical risk, 12 patients underwent esophagectomy (Group 1) and 3 patients underwent additional chemoradiotherapy because of high surgical risk (Group 2). Side effects consisted of nausea, vomiting and myelo-suppression in 8 patients, but all patients tolerated and completed a full course of NAC. The effective rate (CR + PR) of NAC was 58.3% in Group 1 and 66.7% in Group 2. No patients showed pathological CR. Two-year survival rate was 28.1% in Group 1 (PR: 33.3%, NC: 20.0%) and 33.5% in Group 2. This protocol had acceptable toxicities but did not show survival benefit. Further trials are necessary to improve survival rate.
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PMID:[Neoadjuvant chemoradiotherapy for advanced squamous cell carcinoma of thoracic esophagus]. 1475 Mar 20

Gynecologic cancers have been mainly treated by surgery and radiotherapy. Recently, many antineoplastic medications are available and chemotherapy becomes an important therapeutic method in the treatment of cervical, endometrial and ovarian cancer. Platinum derivatives, taxanes, alkylating agents and irinotecan are usually used. Because these chemotherapeutic agents have many toxicities such as myelo-suppression, hypersensitivity reaction, nausea, vomiting and diarrhea, the treatment was scheduled for an inpatient setting. During the recent 10 years, new chemotherapeutic agents without severe toxicity were applied and effective supportive therapies to prevent toxicity were investigated. Under these conditions, chemotherapy in an outpatient setting is available and an Outpatient Chemotherapy Center was established at Kitasato University Hospital. Patients with gynecologic cancers mainly receive weekly chemotherapeutic regimen at the Outpatient Chemotherapy Center and the number is increasing gradually. For safe and comfortable outpatient chemotherapy, it is important to control regimens and to go into partnership with co-medicals.
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PMID:[Outpatient chemotherapy in gynecologic oncology]. 1746 90

Standard post-surgical (adjuvant) chemotherapy for ovarian cancer is based on a platinum salt, and may be repeated if relapse occurs more than six months after the end of chemo- therapy. Olaparib inhibits enzymes involved in DNA repair. It is claimed to have an antitumour effect, especially in the presence of deleterious BRCA muta- tions. Olaparib has been authorised in the EU for continuous single-agent therapy after the end of platinum-based chemotherapy in patients with "plati- num-sensitive" BRCA-positive ovarian cancer who have already received at least two lines of platinum-based che- motherapy and entered complete or partial remission after the last course of treatment. Clinical evaluation of olaparib is based on a randomised, double-blind, placebo-controlled trial in 265 patients who were recruited regardless of their BRCA status. After a median follow-up of 37 months, patients treated with olaparib showed no survival advan- tage, whether or not their tumour harboured BRCA mutations. The time to radiological progression was pro- longed by several months. An inher- ently unreliable post hoc analysis suggested that olaparib delayed the need for further chemotherapy. Olaparib exposes these patients in remission to frequent adverse effects, including nausea, vomiting, and impaired haematopoiesis. Olaparib can also cause life-threatening myelo- dysplastic syndrome, acute myeloid leukaemia, and haemorrhage. Olaparib is metabolised in the liver, mainly by cytochrome P450 isoenzymes CYP3A4 and CYP3A5. It is also a P-glycoprotein substrate and is likely to inhibit CYP3A4, P-glycopro- tein and other carrier proteins. Multiple pharmacokinetic interactions are also likely. Treatment with olaparib requires patients to take eight capsules twice a day, between meals. In practice, in early 2016, expectations of patients with ovarian cancer who have received at least two lines of chemotherapy are high, as they have short life expectancy and no sat- isfactory treatment options. Yet treat- ment with olaparib after the end of platinum-based chemotherapy still has an unfavourable harm-benefit bal- ance: patients derive no proven ben- efit, but adverse effects are frequent and sometimes fatal.
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PMID:Olaparib (LYNPARZAO) Ovarian cancer: spare patients who are in remission. 3073 Jun 34


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