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

Interferon-alfa (IFN-alpha) and cisplatin have shown synergism in vitro against tumour cell lines and optimal effects were observed with continuous and high IFN concentration. 20 patients with advanced malignant melanoma were treated with 10 MU IFN subcutaneously continuously, daily, plus cisplatin 50 mg/m2 intravenously on days 8 and 9. Cisplatin was repeated every 4 weeks. The main toxic effects were myelosuppression, fatigue and weight loss. Toxicities always resolved completely after reduction/interruption of IFN and no life-threatening infection was observed. There were 1 complete and 6 partial responses. 6 patients had stable disease. Median time to progression was 7 months with a range of 16 to 2 months. The combined regimen of IFN-alpha and cisplatin is active in patients with multiple visceral and skeletal sites.
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PMID:Phase II study of continuous subcutaneous interferon-alfa combined with cisplatin in advanced malignant melanoma. 162 70

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
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PMID:A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer. 788 58

Cisplatin, mitomycin C and 5-fluorouracil were given a 55-year-old woman for an unresectable gastric cancer, and successful radical gastrectomy was performed. Postoperative adjuvant immunochemotherapy using UFT and PSK was continued for about 4 years and 4 months. Pancytopenia was observed at 5 years after the treatment and then marked leucocytosis was noted. She also showed complications of general fatigue, appetite loss etc. A secondary acute leukemia associated with eosinophilia was diagnosed by peripheral blood examinations, showing WBC, 122,400: blast, 37.5 % and eosinophil, 41%. Results also showed atypia and pseudo-Pelger nuclear abnormality of eosinophil, high positive stain of cell myelogenic cell surface marker, many numeral and structural abnormalities of chromosomal analysis, etc. From the above results, it was suggested that the leukemia might be induced by previously performed chemotherapy. The patient died about 2 months following its onset.
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PMID:[A case of secondary leukemia induced by chemotherapy with a CDDP-based regimen for gastric cancer 5 years following radical resection]. 842 78

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.
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PMID:Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study. 871 68

The aim of this study was to determine whether it is feasible to reduce the overall treatment time from 7 to 4 weeks in patients with non-small cell lung cancer (NSCLC) receiving radiotherapy with cisplatin. This follows an EORTC phase III randomised trial (08844) in which cisplatin given before each radiation dose resulted in improved local control and survival, but which had a relatively long treatment period of 7 weeks [Schaake-Koning et al., N Engl J Med 1992, 326, 524-530]. 38 patients with confirmed NSCLC (2 stage I, 1 stage II, 18 stage IIIA, 17 stage IIIB) received a total tumour dose of 55 Gy/20 fractions/26 days, from January 1992 to March 1994. Daily fractions of 2 Gy (5 times/week) were given to the macroscopic tumour and the non-involved adjacent lymph node areas. During the same session, a dose of 0.75 Gy was given to the macroscopic tumour (simultaneous boost). Cisplatin 6 mg/m2 was administered 1-2 h before each fraction, in an escalating total dose, during week 1 in 3 patients, during weeks 1 and 2 in 6 patients, during weeks 1, 2 and 3 in 5 patients and during the whole treatment in 24 patients. 38 patients were evaluable for acute side-effects (WHO). Maximal therapy-related toxicity (WHO) was grade 3 (nausea/vomiting in 2 patients, oesophagitis in 3 patients, dyspnoea in 3 patients, cough in 1 patient). Late side-effects were evaluated in 34 patients. There was grade 2 oesophagitis in 2 patients; grade 3 toxicity in 8 patients (tiredness in 3 patients, dyspnoea in 3 patients, oesophagitis in 2 patients); grade 4 toxicity in 4 patients (dyspnoea in 3 patients, cough in 1 patient). Pulmonary fibrosis grade 3 occurred in 4 and grade 4 in 6 patients. One patient developed a severe (grade 3) radiation pneumonitis. The low incidence of acute and late side-effects with this treatment, combining daily administration of 6 mg cisplatin with radical radiotherapy using a simultaneous boost technique, indicates that escalation of the radiation dose seems feasible.
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PMID:Feasibility of escalating daily doses of cisplatin in combination with accelerated radiotherapy in non-small cell lung cancer. 886 92

Cisplatin is a known cause of hemolytic uremic syndrome (HUS). The acute, fulminant form of cisplatin-induced HUS is almost always fatal. We present a 67-year-old Hispanic woman who was treated with cisplatin for squamous cell carcinoma of the tongue. Three days after receiving the treatment, she presented with increasing fatigue, decreased urine output, and confusion. Physical examination was remarkable for tachycardia of 130 beats/min, peripheral edema, and mental obtundation. Laboratory investigations showed a white cell count of 5,500/microL, hemoglobin level of 9.6 g/dL, hematocrit of 29.6%, and platelet count of 13,000/microL. Schistocytes were present on peripheral smear. Screening for disseminated intravascular coagulation was negative. Serum chemistry values included blood urea nitrogen 111 mg/dL, creatinine 3.8 mg/dL, and lactate dehydrogenase (LDH) 927 IU. The patient underwent hemodialysis and therapeutic plasma exchange (TPE), using fresh frozen plasma (FFP). Dialysis was no longer required after the fifth day. TPE was performed daily until the platelet count normalized on the 13th day, after which intertreatment intervals were extended until normalization of LDH levels on the 50th day. We conclude that the normally fatal, fulminant form of cisplatin-induced HUS can be successfully treated with standard TPE, using FFP replacement.
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PMID:Successful treatment of cisplatin-induced hemolytic uremic syndrome with therapeutic plasma exchange. 970 19

Initial clinical results of concurrent chemoradiotherapy combined with high-dose intraoperative radiotherapy (IOR) for locally advanced pancreatic cancer were analyzed. Between June 1996 and May 1999, 6 patients with locally advanced pancreatic cancer without distant metastasis were treated with preoperative concurrent chemoradiotherapy followed by IOR. Preoperative radiation therapy was given by the dynamic arc conformal technique with a daily fraction of 1.8 Gy to a total dose of 45 Gy in 5 weeks. Cisplatin (5 mg/day for 4 weeks) and 5-fluorouracil (250 mg/day for 5 weeks) were administered continuously during preoperative radiation therapy. IOR as a single dose of 28 or 30 Gy was given to the gross tumor volume using electron beams of 15- to 22-MeV. Concurrent chemoradiotherapy was well tolerated, although all of the patients complained of nausea and fatigue. Two patients developed grade III leukopenia. No other serious acute toxicity was noted. The median survival time of the 6 patients was 17.5 months, which was significantly longer than that of our historical control treated with external radiation therapy with IOR (8 months), although the difference in survival was borderline significant (p=0.068). Concurrent chemoradiotherapy followed by high-dose IOR was well tolerated in patients with locally advanced pancreatic cancer, and the initial clinical results appeared promising.
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PMID:Concurrent chemoradiotherapy combined with intraoperative radiotherapy for locally advanced pancreatic cancer: a feasibility study. 1085 42

A phase II study was conducted to assess the response rate and toxicity profile of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol) administered weekly to patients with untreated advanced adeno-carcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction and with adequate liver, kidney, and bone marrow functions were included. Patients were treated with 65 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered intravenously 1 day per week for 4 consecutive weeks, followed by a 2-week recovery period. Response rate, time to progression, survival, and toxic effects were analyzed. Thirty-six (95%) of 38 registered patients were assessable for toxicity and response. The median number of 6-week cycles per patient was 2.5 (range: 1 to 7 cycles). Four patients (11%) achieved a complete response and 17 (47%) had a partial response for an overall response rate of 58%. Median time to progression of carcinoma was 24 weeks, and median survival was 9 months (range: 1 to 23+ months). There was one treatment-related death. Major toxic effects included diarrhea, neutropenia, and fatigue. The combination of irinotecan and cisplatin is active against gastric or gastroesophageal adenocarcinoma and should undergo further study. The addition of other active drugs or radiation therapy to this regimen would be of interest.
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PMID:Irinotecan plus cisplatin in advanced gastric or gastroesophageal junction carcinoma. 1130 42

Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, <or=grade 2; 3% of cycles, >or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.
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PMID:A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. 1171 40

This phase I study was conducted to determine the recommended phase II doses, safety profile, and antitumour activity of a combination regimen of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. Cisplatin and epirubicin were given at fixed doses of 50 and 60 mg m(-2), respectively. The irinotecan dose was escalated at 10 mg m(-2) increments from a starting dose level of 70 mg m(-2). Epirubicin, irinotecan, and their metabolites were measured with HPLC methods. In all, 35 patients received 141 courses of treatment. Irinotecan dose was escalated in seven cohorts up to 130 mg m(-2), and then finally de-escalated to 110 mg m(-2). The dose-limiting toxicity was neutropenic fever. Nonhaematologic toxicities included mild to moderate nausea/vomiting, diarrhoea and fatigue. Of 34 patients with evaluable disease, one patient had a complete response and nine patients had partial response, yielding an overall response rate of 29.4%. Pharmacokinetic parameters of epirubicin were not affected by the sequence of drug administration. However, the AUCs of irinotecan and its metabolites were increased significantly when irinotecan and epirubicin were administered concurrently. This combination regimen has promising broad antitumour activity, and will be further evaluated in phase II studies in multiple tumour types.
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PMID:Phase I study of cisplatin, irinotecan, and epirubicin administered every 3 weeks in patients with advanced solid tumours. 1291 67


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