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)

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.
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PMID:Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II. 1253 29

In patients with advanced breast cancer, treatment with paclitaxel and doxorubicin has been shown to produce impressive overall response rates (up to 94%) and to prolong overall survival significantly over a combination of fluorouracil (5-FU), doxorubicin, and cyclophosphamide (Cytoxan, Neosar) in one prospective phase III clinical study. These results have been challenged, however, by other data demonstrating no survival advantage for taxane-based therapies. In addition, the combination of paclitaxel and doxorubicin has repeatedly been shown to be complicated by the development of treatment-related congestive heart failure, when cumulative doxorubicin doses exceed 300-360 mg/m2. Consequently, attempts have been made to increase the complete remission rate and overall survival resulting from first-line treatment of metastatic breast cancer without compromising patient safety. Gemcitabine (Gemzar)--a relatively effective, well-tolerated and partially non-cross-resistant antitumor compound with limited toxicity--represents an attractive alternative to paclitaxel/anthracycline combinations. Initial studies of combination therapy with gemcitabine and paclitaxel have produced an average response rate of 52%, with time to progression ranging between 7.0 and 14.5 months. Three-drug regimens containing gemcitabine, an anthracycline, and paclitaxel have been tested in phase II studies and have produced impressive response rates of 82.9% with gemcitabine, doxorubicin, and paclitaxel and 92% with gemcitabine, epirubicin (Ellence), and paclitaxel (GET). The Central European Cooperative Oncology Group has evaluated the GET regimen vs a regimen containing 5-FU, epirubicin, and cyclophosphamide (FEC) in a randomized, prospective phase III study. Interim toxicity analysis showed that the GET regimen was well tolerated but produced more grade 4 neutropenia (64% vs 42%, P = .084) and significantly more grade 4 thrombocytopenia (12% vs 0%; P < .001) than FEC. Anaphylactic/allergic reactions, peripheral polyneuropathy, nausea, and cardiotoxicity constituted rare events and did not exceed grade 1 or 2 in severity. Although final data from this phase III trial are not yet available, preliminary analysis suggests the GET regimen represents an attractive option for patients with advanced breast cancer.
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PMID:Gemcitabine, anthracycline, and taxane combinations for advanced breast cancer. 1476 4