Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LY188011 (Gemcitabine hydrochloride) is a new derivative of deoxycytidine. Phase I study was carried out by a cooperative study group. LY188011 was administered weekly for 3 consecutive weeks starting with an initial dose of 60 mg/m2 (1n) and then increasing the dosage to 1,000 mg/m2 (16.7n). Dose limiting factor was found to be myelosuppression (decreases of WBC, neutrophils and platelet), and MTD was considered to be 1,000 mg/m2. The nadir of WBC and platelet were observed after about 1-3 weeks. It took 1-2 weeks for their recovery. Other adverse reactions included fever, fatigue, anorexia, nausea/vomiting, anemia and transient elevations of GOT and GPT. However, those adverse reactions were mild. T1/2 rho of plasma concentration was about 19 min and the C5min was dependent on the dose. Anti-cancer effects were observed in one gastric cancer and two colon cancer patients. It is recommended that the dosing schedule for an early phase II study is 800 mg/m2 weekly for 3 weeks with 1 week of rest as one cycle, in multiple cycles.
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PMID:[LY188011 phase I study. Research Group of Gemcitabine (LY188011)]. 868 15

In our previous phase I/II studies, both the cisplatin (Platinol), gemcitabine (Gemzar), and vinorelbine (Navelbine) (PGV), and cisplatin, gemcitabine, and paclitaxel (Taxol) (PGT) regimens produced a median survival of approximately 1 year in patients with advanced non-small-cell lung cancer (NSCLC). The present phase III study compared the median survival of patients treated with these triple-drug regimens to that of patients receiving cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG). Accrual for the trial began in 1997 and by December 1998, a total of 240 patients (stage IIIB, 98; stage IV, 142) had been enrolled. An interim survival analysis was performed in April 1999. Overall, 151 patients had died. The median survival rates of patients in the PGV, PG, and PV arms were 51, 42, and 35 weeks, respectively. At the time of this analysis, the median survival of patients in the PGT arm could not be assessed; however, the 1-year projected survival rate was 58%. At multivariate Cox analysis, the estimated risk of death for patients receiving PGV compared with those receiving PV was 0.35 (95% CI, 0.16-0.77, P = .0058). Overall response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm, and 58% in the PGT arm. Severe neutropenia and vomiting were significantly more frequent in patients who received PV than in those who received PGV. The PV regimen produced a significantly shorter survival compared with the PGV combination. Since this difference in survival complied with one of the early stopping rules, accrual in the PV arm was discontinued. Enrollment in the PGV, PG, and PGT arms is ongoing.
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PMID:Interim analysis of a phase III trial. Triple- vs double-agent chemotherapy for advanced non-small-cell lung cancer. Southern Italy Cooperative Oncology Group. 1096 Sep 44

In a randomized phase III trial, 343 patients with advanced non-small cell lung cancer aged <or=70 years with good performance status received a new triplet regimen consisting of cisplatin at 50 mg/m(2), gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) at 1,000 mg/m(2), and vinorelbine at 25 mg/m(2) on days 1 and 8 every 3 weeks (PGV); a doublet of cisplatin at 100 mg/m(2) on day 1 and gemcitabine at 1,000 mg/m(2) on days 1, 8, and 15 every 4 weeks (PG); or a newly developed triplet combination of cisplatin at 50 mg/m(2), gemcitabine at 1,000 mg/m(2), and paclitaxel at 125 mg/m(2) (over 1 hour) on days 1 and 8 every 3 weeks (PGT). Response rates were 44% in the PGV group, 48% in the PGT group, and 28% in the PG group (P < .02 for both PGV and PGT v PG). Median survival durations were significantly increased in both the PGV and PGT groups compared with the PG group (51 weeks for both v 38 weeks; P < .05 for both). Times to disease progression were increased in both the PGV (24 weeks) and PGT (29 weeks) groups compared with the PG group (19 weeks) (PGT v PG; P < .002). Both triple-agent combinations were well tolerated. Among hematologic toxicities, severe thrombocytopenia was more common in the PG arm than in the PGT group. Severe vomiting was more common in the PG arm than in either triplet group, whereas mild neuropathy was more common in the triple-agent arms and grade 3 fatigue was more common in the PGT group than in the PG arm. In summary, the new PGV and PGT triplet regimens were associated with improved outcome in patients with advanced non-small cell lung cancer with good performance status, without an increase in major toxicity. Semin Oncol 28 (suppl 7):7-10.
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PMID:Phase III trial of cisplatin/gemcitabine with or without vinorelbine or paclitaxel in advanced non-small cell lung cancer. 1137 45

Pemetrexed (Alimta; Eli Lilly and Co, Indianapolis, IN) is a multitargeted antifolate that inhibits several folate-dependent enzymes that play roles in purine and pyrimidine synthesis. The principal toxicities of pemetrexed are neutropenia, diarrhea, nausea/vomiting, mucositis, and skin rash. These toxicities are more frequent in vitamin-deficient (folate and vitamin B 12 ) patients, and can be ameliorated by the co-administration of folate and vitamin B 12 . The use of prophylactic dexamethasone is also recommended to reduce the frequency of severe skin rash. Pemetrexed has significant single-agent activity in previously treated and untreated patients with non-small cell lung cancer (NSCLC). A recent phase III trial comparing pemetrexed with docetaxel in previously treated NSCLC patients showed equivalent efficacy with less bone marrow toxicity (eg, neutropenia) in the pemetrexed group. These results were pivotal in the approval of pemetrexed for the treatment of refractory NSCLC. Pemetrexed has been combined with the platinums (ie, cisplatin, carboplatin, and oxaliplatin) in NSCLC to yield clinical activity similar to that of other platinum-based doublets. A comparative phase III trial of cisplatin/pemetrexed against cisplatin/gemcitabine (Gemzar; Eli Lilly and Co) is under way. Pemetrexed has also been evaluated in combination with gemcitabine, and although the optimal dose and schedule of this combination has not been defined, clinical activity similar to other nonplatinum-based doublets has been observed. Preliminary evidence suggests that pemetrexed can be combined with thoracic radiation therapy, but more data are needed to evaluate the potential advantage(s) pemetrexed may have in this setting. Pemetrexed/platinum doublets also appear to possess activity in extensive stage small cell lung cancer. A phase II trial of single-agent pemetrexed is under way in both sensitive- and refractory-relapsed small cell lung cancer. Given the activity and excellent tolerability of pemetrexed, further studies in lung cancer are warranted.
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PMID:The evolving role of pemetrexed (Alimta) in lung cancer. 1581 33