Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-nine patients with recurrent or advanced, incurable head and neck cancer were entered into a phase I-II trial of carboplatin in combination with 5-fluorouracil (5-FU), 1,000 mg/m2/d continuous intravenous (IV) infusion for five days every 28 days. The initial dose of carboplatin was 300 mg/m2 for patients with Karnofsky performance scores greater than or equal to 70%, and 240 mg/m2 for patients with scores of 50% to 60%. Subsequent doses were modified to achieve grade 2 myelo-suppression: WBC, 2,000 to 2,999 cells/microL; granulocytes, 1,000 to 1,499 cells/microL; and platelets, 50,000 to 75,000 cells/microL. Dose levels were 180, 240, 300, 360, and 420 mg/m2. Twenty-eight patients had squamous-cell cancers and one had an adenoid cystic carcinoma of the parotid. There were 26 patients with recurrent disease; 22 had received prior RT; only two had received other chemotherapy immediately before study entry. Three patients had newly diagnosed incurable stage IV disease. The median performance status was 80% (range, 60% to 90%). All patients had objectively measurable disease, and 28 were evaluable for response. There were three complete responses (CRs) and ten partial responses (PRs) (48% CR and PR); the median duration of response was 4.7 months (range, 1.5 to 15+ months). Dose-limiting toxicities were granulocytopenia, thrombocytopenia, and stomatitis. Prolonged myelosuppression delayed retreatment in eight patients and delayed 19 of 107 (18%) courses. Stomatitis occurred in 61% and diarrhea in 29%. 5-FU dosage was decreased in ten patients (36%) for grade 2 or greater stomatitis or diarrhea. Mild to moderate nausea and vomiting occurred in 66% of patient trials in which no pretreatment antiemetics were administered. Other toxicities included phlebitis from 5-FU in 71%, skin toxicity in 11%, mild alopecia in 25%, and fatigue in 54% of patients. Nephrotoxicity (creatinine greater than 2.0 mg/dL) occurred in one patient. The dose of carboplatin resulting in grade 2 toxicity was 180 mg/m2 in one patient, 240 mg/m2 in one, 300 mg/m2 in seven, 360 mg/m2 in ten, and 420 mg/m2 in one. Based on these results, we recommend a starting dose of carboplatin, 300 mg/m2, in combination with five days of continuous infusion 5-FU. In this dose and schedule, this combination was well tolerated and demonstrated antitumor activity in head and neck cancer. To confirm these promising results, a Southwest Oncology Group prospective randomized trial is in progress comparing carboplatin and 5-FU, cisplatin and 5-FU, and standard-dose weekly methotrexate in recurrent-disease patients.
 ...
PMID:A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck. 354 42

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.
 ...
PMID:Alpha-2-interferon/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. 369 41

Triglycidylurazol is a teroxirone derivative proposed for clinical trials on the basis of a broad spectrum of activity against murine tumors and a reduced potential for toxic manifestations at the injection site as compared to the parent compound. This phase I trial was designed to define the maximum tolerated dose of triglycidylurazol given by iv bolus on a 5-day schedule. Twenty-eight adult patients with a variety of solid tumors were entered. Their median performance status was 2 (range, 0-3), and most had received prior radiotherapy, chemotherapy, or both. A median of one course (range, one to four) was administered, for a total of 47 courses. Doses were escalated from 6 to 250 mg/m2/day. Leukopenia and thrombocytopenia were dose-related and -limiting, with a strong suggestion of increased myelosuppression with repeated courses. Nonhematologic toxic effects were generally mild to moderate. Nausea and vomiting were experienced by most patients. Local toxic effects consisting of venous discoloration, phlebitis, and/or sloughing were encountered in about one-half of the patients. Possible drug-related impairments in liver function were noted in three patients. Negligible alopecia and fatigue were also observed. Antitumor effect was detected in one patient with adenocarcinoma of unknown origin. A dose of 200 mg/m2/day for 5 consecutive days may be recommended for phase II trials.
 ...
PMID:Phase I study of triglycidylurazol given on a 5-day i.v. schedule. 370 9

A co-operative phase II study of the semisynthetic podophyllotoxin derivative Etoposide (VP-16) was undertaken in patients with genitourinary tumors. A total of 83 out of 115 patients entered into the study were evaluable for response. Antitumor effects were evaluated according to "Standards for the Evaluation of Direct Effects of Chemotherapy in Solid Tumors" (otherwise known as the Koyama-Saito Group Criteria). Objective response was noted in 2 patients (6.3%) out of 32 with testicular cancer, whereas no responders were seen in bladder and renal cancer patients. In patients with prostatic cancer, 1 out of 13 (7.7%) responded. Major clinical side effects were alopecia and gastrointestinal toxicities (anorexia, nausea and vomiting). Mucositis, abdominal pain, diarrhea and general fatigue were also noted. Anomalies in laboratory test findings were mainly myelosuppression-related, with leukopenia being observed in 66.3% of patients.
 ...
PMID:[Phase II study of etoposide (VP-16-213) in genitourinary tumors. VP-16-213 Genitourinary Study Group]. 375 24

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
 ...
PMID:The new alpha interferons. 391 Mar 84

Interferons manifest diverse immunomodulatory and antiproliferative characteristics. Since their spectrum of toxicities includes primarily fatigue and anorexia rather than the myelosuppression concomitant with cytotoxic therapies, it is conceptually appealing to combine both modalities. We conducted a phase I trial among 18 patients using the combination of leukocyte A recombinant interferon (IFN-rA) and BCNU. The intramuscular (IM) IFN-rA dose for the initial 12 patients was 12 X 10(6) U/m2 three times a week for an anticipated duration of 12 weeks. Among these patients, we escalated the monthly intravenous (IV) BCNU dose from 50 mg/m2 to 150 mg/m2. Six subsequent patients received IFN-rA 12 X 10(6) U/m2, days 1 to 3, and BCNU 150 mg IV on day 3 of each monthly cycle. Dose-limiting toxicities from both regimens were fatigue and myelosuppression. We recognize the limitation of small sample sizes. Nevertheless, in the absence of a significant number of life-threatening toxicities, it appears that near maximal doses of BCNU and concomitant IFN-rA can be administered with safety in an outpatient setting.
 ...
PMID:Phase I study of recombinant leukocyte A human interferon combined with BCNU in selected patients with advanced cancer. 395 Jun 78

A phase I study of weekly iv thymidine (TdR) and 5-FU was carried out in patients with advanced colorectal carcinoma using two dosage schedules. Schedule 1 employed a 3-hour infusion of TdR (6-8 g/m2/hour) followed immediately by a bolus of 5-FU (100-200 mg/m2). Schedule 2 used a slightly larger dose of TdR (18 g/m2/hour for 1.5 hours), with 5-FU given 30 minutes after the TdR infusion was started. Myelosuppression was observed erratically at the higher doses of 5-FU. Diarrhea and severe fatigue were seen frequently with Schedule 1. CNS side effects were the dose-limiting effects for both schedules. For long-term use the maximally tolerated 5-FU doses were 100 mg/m2/week for Schedule 1 and 175 mg/m2/week for Schedule 2. In pharmacokinetic studies in five patients, both schedules produced prolonged plasma beta-half-lives of 5-FU (96-189 minutes). Extensive formation of floxuridine was seen with both schedules. It appears likely that CNS toxic effects are characteristic of TdR-containing 5-FU regimens and would limit the therapeutic potential of this approach.
 ...
PMID:Phase I evaluation and pharmacokinetic study of weekly iv thymidine and 5-FU in patients with advanced colorectal carcinoma. 397 91

It is unclear from preliminary laboratory studies whether a high- or a low-dose interferon treatment strategy is optimal. As part of an ongoing study of mechanisms of interferon action, we have evaluated toxicity in a two-arm protocol in which patients were randomly assigned to receive lymphoblastoid interferon by either a low-dose treatment strategy (2 X 10(6) units/m2 daily X 28 days then daily X 5 days every other week by im injection) or a high-dose treatment strategy (5 X 10(6) units/m2 by continuous iv infusion over 24 hours, escalating by 5 X 10(6) units/m2/day as tolerated over 10 days, repeated every 28 days). The main toxic effects in both arms were fever, fatigue, and anorexia. Marked interpatient differences within each dose arm were greater than differences between arms. Additional significant toxic effects included nausea and vomiting, hypotension, leukopenia, thrombocytopenia, and evidence of hepatic toxicity. Minor changes in serum electrolytes were noted. Coagulation studies were normal. The dose-limiting toxic effect for the high-dose arm was myelosuppression. Median maximum tolerated dose among high-dose strategy patients was 18 X 10(6) units/m2, but there was marked interpatient variation. We conclude that both dose schedules were relatively well-tolerated. Because of individual variation in tolerance, high-dose treatment should include a dose escalation strategy.
 ...
PMID:Prospectively randomized toxicity study of high-dose versus low-dose treatment strategies for lymphoblastoid interferon. 401 85

Recombinant leukocyte alpha interferon (rIFN-alpha A; Hoffmann-La Roche, Inc) was administered to 15 patients with recurrent or persistent ovarian carcinoma. All patients had been previously treated with surgery and combination chemotherapy including cyclophosphamide (15 patients), doxorubicin (14), and cisplatin (14). Three patient had also previously undergone radiation therapy. At the start of therapy the largest tumor size was less than or equal to 2 cm in four patients and greater than 2 cm in 11. Interferon was administered in three times weekly for 8 weeks at a dose of 20 X 10(6) units/m2, with average drug levels of 2267 pg/ml 6 hours after im injection. In three patients (20%), the dose had to be reduced by 50% because of drug toxicity. Side effects included fever (greater than 101 degrees F) in 12 patients, fatigue in ten, headache in two, diarrhea in two, and reversible myelosuppression in five. Of the 15 patients, one had mixed response lasting 12 weeks, two had stable disease of 8 weeks' duration, and 12 had disease progression.
 ...
PMID:Recombinant leukocyte alpha interferon in advanced ovarian carcinoma. 401 97

Thirty-eight patients with advanced breast cancer, multiple myeloma, and malignant lymphoma were treated with partially purified (about 0.1%) leukocyte interferon. Patients were treated with a remission-induction schedule of 3 million to 9 million antiviral units daily intramuscularly for 4 to 26 weeks. Responding patients were maintained on a schedule of 3 million U three times weekly. Tumor regression was observed in seven of 17 patients with breast cancer. Six of 10 patients with multiple myeloma responded with a decrease of at least 50% in serum myeloma protein levels or Bence Jones protein excretion. Six of the 11 lymphoma patients achieved tumor regression. Complete remissions occurred in two patients. Of the 19 responding patients, five remain on study for 52 to 63 weeks. Toxicity included low-grade fever, fatigue, anorexia, and partial alopecia. Myelosuppression (lowest median leukocyte count, 2500/mm3; granulocytes, 1300/mm3) occurred in most patients. On the basis of this pilot study, we conclude that leukocyte interferon can induce tumor regression in patients with advanced cancer.
 ...
PMID:Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. 615 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>