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)

To determine the activity and toxicity of gemcitabine in non-small cell lung cancer, three phase II studies of single agent gemcitabine have been conducted between 1990 and 1994. In an early phase II study, gemcitabine was administered of 800 mg/m2 on day 1, 8, 15 every four weeks (step I), and 1,000 mg/m2 (step II). Response was observed in 3 of 13 patients with previously untreated non-small cell lung cancer, although there was no responders in the previously treated patients. Late phase II studies were performed at 20 (group A) and 24 (group B) Japanese institutions to confirm the efficacy and safety of gemcitabine administered alone in patients with non-small cell lung cancer. Seventy-three patients (group A) and 67 patients (group B) were entered into these studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response in group A. Of 67 patients, 14 (20.9%) showed a partial response in group B. Grade 3 or greater toxicities included anemia (20.5%) and leukopenia (9.6%) in group A, and in 13.4% and seven 10.4% in group B, respectively. And grade 3 thrombocytopenia was observed in 1.4%. Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of ARDS. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility in advanced non-small cell lung cancer on an outpatient basis. Further trials in combination with other active agents are warranted.
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PMID:[Phase II studies of gemcitabine for non-small cell lung cancer in Japan]. 1039 14

The activity and mild toxicity profile of single-agent gemcitabine therapy in untreated (chemonaive) patients with non-small-cell lung cancer (NSCLC) is well documented. This phase II trial was conducted to determine the objective tumour response rate and toxicity profile of single-agent gemcitabine in pretreated patients with NSCLC. Patients with histological evidence of advanced NCSLC stage IIIB or IV; at least one prior chemotherapy regimen including a platinum or taxane analogue; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; clinically measurable disease; adequate bone marrow reserve; and adequate renal function; received 1000 mg m(-2) gemcitabine administered over 30 min on days 1, 8 and 15 of a 28-day cycle defined as 3 weekly treatments followed by 1 week of rest. Twenty-nine patients were evaluated for efficacy and 32 for toxicity. One patient achieved a complete response and five patients had a partial response resulting in a total response rate of 20.6% (95% confidence interval (CI) 6-34). Median response duration was 7 months (range 4-11 months). Twelve (41%) patients reached stable disease after two cycles of therapy and 11 (38%) patients had disease progression. Median progression-free survival time was 3 months and median overall survival time was 5.5 months. Toxicity was generally mild (grades 0-2). Severe (grade 3 or 4) haematological toxicities included grade 3 anaemia in one patient and grade 3 thrombocytopenia in two patients. Severe non-haematological toxicities included one patient each with grade 3 liver transaminase elevations, nausea/vomiting and diarrhoea. This study confirms the activity and safety of single-agent gemcitabine in pretreated patients with advanced NSCLC who are refractory or sensitive to first-line therapy.
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PMID:Single-agent gemcitabine in pretreated patients with non-small-cell lung cancer: results of an Argentinean multicentre phase II trial. 1055 56

For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the addition of oxaliplatin (85 or 100 mg/m2) to bimonthly LV-5-FU has given a response rate of 20-46%. The highest response rate has been observed with oxaliplatin 100 mg/m2 (FOLFOX2). The present phase II study (FOLFOX6) infused oxaliplatin (100 mg/m2) with LV (400 mg/m2) as a 2-h infusion on day 1, followed by bolus 400 mg/m2 and a 46-h infusion (2.4-3 g/m2) of 5-FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial responses (95% confidence interval: 15-38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOLFOX6, median progression-free survival was 5.3 months and median survival 10.8 months. From the 448 cycles analysed, NCI-CTC grade 3-4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, diarrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 (46%) patients experienced grade 3-4 toxicities. Because of toxicity, only 36% of the patients received > or = 90% of the scheduled oxaliplatin dose intensity. FOLFOX6 was active in pretreated patients resistant to LV-5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity and a lower 5-FU dose.
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PMID:Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR. 1065 24

In a multi-institutional Phase II trial, we evaluated the efficacy of a platelet-derived growth factor receptor (PDGF-r) inhibitor, SU101, in patients with hormonerefractory prostate cancer. The patients received a 4-day i.v. loading dose of SU101 at 400 mg/m(2) for 4 consecutive days, followed by 10 weekly infusions at 400 mg/m(2). The primary study end points were a decline in prostate-specific antigen (PSA) and a decrease in measurable tumor. Secondary end points were time to progression and an effect on pain as measured by the Brief Pain Survey. Expression of PDGF-r was examined in both metastatic and archival primary prostate tumor samples. Forty-four patients were enrolled at four centers. The median age was 72 years, the median PSA was 223 ng/ml, and 21 patients had at least one prior chemotherapy. Thirty-nine patients are evaluable for PSA, and three patients demonstrated a PSA decline >50% from baseline (55-99.9% decrease). The median time to progression was 90 days. Of 19 patients evaluable for measurable disease, 1 patient had a partial response. Nine of 35 evaluable patients had significant improvement in pain. The most frequent adverse events were asthenia (75%), nausea (55%), anorexia (50%), and anemia (41%). PDGF-r expression was detected in 80% of the metastases and 88% of primary prostate cancers. The results of this trial may warrant further clinical studies with other PDGF-r inhibitors.
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PMID:A multi-institutional phase ii study of SU101, a platelet-derived growth factor receptor inhibitor, for patients with hormone-refractory prostate cancer. 1130 25

Malignant melanoma is increasing in frequency at a rapid rate in the United States. Metastatic disease is chemoresistant with DTIC considered the most active single agent. CI-980 is a synthetic mitotic inhibitor that blocks the assembly of tubulin and microtubules. It has shown cytotoxic activity against a broad spectrum of murine and human tumor cell tines. CI-980 can cross the blood brain barrier, is effective when given orally or parenterally, and is active against multidrug resistant cell lines overexpressing P-glycoprotein. In this trial, patients with disseminated melanoma with measurable disease, SWOG performance status of 0-1, no prior chemotherapy or immunotherapy for metastatic disease, and adequate hepatic and renal function, were enrolled. Treatment with CI-980 was given by 72 h continuous i.v. infusion at a dose of 4.5 mg/m2/day, days 1-3 every 21 days. Twenty-four patients were registered on this study with no patients ineligible. They ranged in age from 33-78 with performance status of 0 in 15 patients and 1 in 9 patients. Nineteen patients had visceral disease with 12 having liver involvement. There were no confirmed responses. The overall response rate was 0% (95% CI 0%-14%). The median overall survival is eleven months (95% CI 4-14 months). The most common toxicities were hematologic and consisted of leukopenia/granulocytopenia and anemia, with nausea/vomiting and malaise/fatigue/weakness also frequent. CI-980 administered at this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.
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PMID:Phase II trial of CI-980 in patients with disseminated malignant melanoma and no prior chemotherapy. A Southwest Oncology Group study. 1156 81

The combination of docetaxel and estramustine has exhibited synergistic activity both in prostate cancer cell lines and in patients with hormone-refractory prostate cancer (HRPC). Based on these promising preclinical and phase I/II data, we conducted a study of weekly docetaxel and estramustine in patients with metastatic HRPC and a poor performance status. A total of 30 patients received (1) a 3-day course of oral estramustine during weeks 1 and 2 of each 3-week cycle plus (2) docetaxel, 35 mg/m(2) intravenously on day 2 of weeks 1 and 2. The median number of cycles per patient was 5, ranging from 1 to 22. The median patient age was 74 years (range, 61 to 90 years), and the median baseline Karnofsky performance status was 60% (range, 50% to 80%). Twenty-three patients (76%) had a > or =50% decrease in serum prostate-specific antigen (PSA); 17 (56%) of these patients had a > or =75% decrease in PSA. Pain scores and performance status likewise improved in 70% of patients. Three complete responses and four partial responses were observed among 12 patients with measurable disease. Toxicities were primarily nonhematologic in nature, with the most common being grade 1 through 3 nausea, asthenia, diarrhea, and edema. Given the activity and tolerability of weekly docetaxel and estramustine in this study, this regimen appears to be more suitable than previously studied docetaxel/estramustine administration schedules for treating metastatic HRPC in elderly patients with a poor performance status.
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PMID:Weekly docetaxel and estramustine in patients with hormone-refractory prostate cancer. 1168 24

Advanced renal cell carcinoma is a chemoresistant disease. Immunotherapy with alpha interferon or interleukin (IL)-2 has produced response rates of approximately 15%, but better treatments are needed. IL-4 is a cytokine produced by activated CD4+ lymphocytes and has pluripotent activities including inhibiting the in vitro proliferation of human renal cell carcinoma cell lines. In this trial, patients were required to have a histologic diagnosis of renal cell adenocarcinoma with measurable disease and performance status (SWOG) of 0-1. Patients had to have adequate bone marrow, renal, and hepatic function as well as no clinically significant pulmonary or cardiac dysfunction. IL-4 was given by subcutaneous injection at a dose of 5 micorg/kg/d, daily for 28 days followed by a 7-day rest period. Fifty-eight patients were registered with seven patients ineligible and two patients not analyzable because they did not receive treatment. In the 49 eligible and analyzable patients, there were no confirmed complete or partial responses. There was one unconfirmed partial response in retro-caval lymph nodes, but no verifying measurement was done. There were seven patients with stable disease, no response, 25 with increasing disease/progression, and 16 patients whose assessment was inadequate to determine response. The median time to progression was 3 months, and the median survival was 13 months. Toxicity was significant with the most common side effects nausea, vomiting, or diarrhea, followed by headache/pain and malaise/fatigue/lethargy. There were 13 instances of grade 4 toxicity that occurred in nine different patients. Unique toxicities included Bell's palsy in three patients and hypoglycemia in a previously well-controlled diabetic. Despite promising growth inhibitory and immunologic effects, IL-4 in this dose and schedule is not useful for the treatment of patients with disseminated renal cell carcinoma.
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PMID:Phase II trial of recombinant human interleukin-4 in patients with advanced renal cell carcinoma: a southwest oncology group study. 1214 58

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.
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PMID:Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer. 1244 53

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

The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation Program, National Cancer Institute) has broad preclinical anti-neoplastic activity. Preliminary data from phase I study demonstrated antitumor activity in colorectal carcinoma. This phase II trial evaluates its efficacy in patients with minimally treated metastatic colorectal cancer. Eligibility included Karnofsky performance status > or = 70%, age > or = 18 years and bidimensionally measurable disease. Thirteen patients were treated with NSC 655649 at 500 mg/m2 by central venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median [range] 2 [1-6]) of therapy were administered. Twelve patients are eligible for response assessment. No major objective responses were seen using the RECIST criteria; however stable disease was observed in three patients with mean duration of 15 weeks. The median time to progression was 8 weeks. There was no toxic death. Four patients received only one cycle of treatment, and three had disease progression. Toxicities were tolerable and hematologic toxicity was the most common. The median (range) granulocyte and platelet nadir counts were 2043/microl (116-16,374/microl) and 276 x 10(3)/ microl (5-769), respectively. Non-hematologic toxicities were moderate, including generalized weakness/fatigue, nausea/vomiting, diarrhea and anorexia. One patient required dose reduction; three patients required dose delays. NSC 655649 at this dose and schedule is inactive against advanced previously minimally treated metastatic colorectal cancer and further study of this drug as a single agent in this disease using an every three-week schedule is not warranted.
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PMID:A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic colorectal cancer. 1279 35


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