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)

This is a phase I-II study of lymphoblastoid interferon (IFN-alpha-N1) combined with primary chemotherapy after cytoreductive surgery in patients with suboptimal stage III and stage IV epithelial ovarian carcinoma. Fourteen patients were treated initially with cyclophosphamide, doxorubicin, and cisplatin (CAP regimen) for two cycles, and IFN (alpha-N1) was added to this combination on day 2 of the third cycle. Patients then were divided into four groups, each group receiving differing doses of IFN ranging from 3 to 10 MU/m2 on each of days 2-5. A total of eight courses of chemotherapy was administered, six of which included interferon. Severe fatigue and malaise were the greatest dose-limiting toxicities associated with the interferon. However, severe bone marrow suppression also limited the administration of interferon. The results of this study suggest that the addition of interferon to the multiagent chemotherapy regimen of CAP is both unacceptable to patients and excessively toxic to the bone marrow. Because of the small patient sample and poor tolerance of the treatment, an accurate evaluation of therapeutic response could not be performed.
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PMID:Human lymphoblastoid interferon (IFN-alpha-N1) plus doxorubicin, cyclophosphamide, and cisplatin in the treatment of advanced epithelial ovarian malignancies. A phase I-II study of the Gynecologic Oncology Group. 198 44

Thirty-nine patients with epithelial ovarian cancer admitted to the Division of Medical Oncology of the Medical School II of Naples were given 159 courses of alpha 2b interferon (30 Mil./sqm IU) intraperitoneally from October 1986 to November 1989. IFN was generally administered every three weeks, but six patients received the drug weekly at the same dose, for an additional period. In 15 patients IFN was added to standard systemic chemotherapy as first line treatment; the remaining patients, all pretreated (22 with minimal and 2 with no residual disease), received an intraperitoneal multidrug treatment combining IFN, cisplatin and mitoxantrone. Peritoneal access was achieved through a temporarily implanted 18 gauge catheter and the drug was instilled in a large fluid volume (2,000 ml) to ensure wide spread and uniform distribution. IFN was well tolerated: only one patient had to discontinue treatment because of severe fatigue. No major complication related to catheter implantation or function occurred. 3/15 untreated and 11/20 pretreated patients, evaluable for response, achieved a pathological complete response (pCR). In view of IFN's lack of significant toxicity and the safety and tolerability of a temporary small gauge catheter for peritoneal access, intraperitoneal chemotherapy including IFN should be useful in ovarian cancer patients with minimal or absent disease after first-line systemic treatment.
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PMID:Alpha 2b interferon (IFN) by intraperitoneal administration via temporary catheter in ovarian cancer. Preliminary data. 205 Jan 63

As previously reported, cytotoxic synergy is produced when clinically achievable concentrations of cytarabine (Ara-C) and hydroxyurea (HU) are used as potential inhibitors of in vitro DNA repair in cisplatin (cis-Pt)-treated human colon carcinoma cells. This pilot study was subsequently designed to duplicate the in vitro dose and schedule and to determine the toxicity of this three-drug combination in two cohorts of patients. 21 patients had received prior chemotherapy and 19 were not previously treated. All patients had refractory solid tumors. They received monthly cycles of an oral loading dose of 800 mg/m2 HU followed every 2 h by 6 oral doses of 400 mg/m2, a 12-h continuous infusion of 200 or 250 mg/m2/h Ara-C concurrent with the HU, and then 100 mg/m2 cis-Pt over 1 h. A total of 95 cycles were given with the expected toxicities of nausea and vomiting and fatigue but not major acute toxicity observed. Thrombocytopenia was significant but transient and was dose-limiting only for patients who had received prior therapy. The median platelet nadir after one cycle was 43,000/microliters for all patients and 67,000/microliters for those who had not undergone prior treatment. Azotemia was treatment-limiting in responding and stable patients, suggesting the possibility of synergistic nephrotoxicity. Interestingly, there were early transient rises in both uric acid and lactate dehydrogenase (LDH). Partial responses were seen in 9 of 32 patients with measurable disease and there was significantly improvement in 5 of 8 patients with only evaluable disease. The responses or improvement occurred in patients with non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma. Of these 14 patients, 9 had failed prior chemotherapy regimens. Significantly, responses were observed in 3 of 8 patients who had previously received cis-Pt, suggesting that the HU/Ara-C combination modulated cis-Pt resistance. Because of these encouraging results, a second pilot study has been initiated with modifications dictated by the toxicity issues raised in this trial.
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PMID:Cisplatin preceded by concurrent cytarabine and hydroxyurea: a pilot study based on an in vitro model. 224 91

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Twenty-four patients with advanced and therapy-resistant ovarian carcinoma were treated with escalating daily doses of human leukocyte interferon (IFN). Doses ranged from 3 X 10(6) to 27 X 10(6) IU/day. Fatigue, fever, thrombocytopenia, and leukopenia were the limiting factors in the escalation of doses. Of nine patients treated for at least 2 months, there were two patients with partial remissions and six with stable disease. Ascites production present in four patients became reduced in three. The level of 2',5'-oligoadenylate synthetase in peripheral blood lymphocytes increased following initiation of IFN therapy. We conclude that IFN-alpha can exert an antitumor effect in some patients with ovarian carcinoma that have previously failed on other therapy regimens.
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PMID:A phase II study on escalating interferon doses in advanced ovarian carcinoma. 327 73

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.
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PMID:Recombinant leukocyte alpha interferon in advanced ovarian carcinoma. 401 97

Fourteen patients with advanced ovarian carcinoma previously treated with chemotherapeutic agents including cisplatin were treated with vinblastine 0.1 mg/kg intravenously every week. There were no responses in 13 evaluable patients. The median survival was 19+ weeks following the initiation of vinblastine (VBL) therapy. Toxicity consisted of minimal myelo-suppression (WBC count less than 2500/microliter in 8/78 courses, WBC count less than 1500/microliter in 0/78 courses, platelets less than 150,000/microliter in 0/78 courses), nausea (4/13 patients), vomiting (2/13 patients), neuropathy (4/13 patients), and weakness and fatigue (6/13 and 5/13 patients, respectively). Although data derived from the human tumor stem cell assay (HTSCA) suggest that VBL may be an active agent against previously treated ovarian carcinoma, this study in patients with refractory advanced disease suggests that VBL is inactive (less than 20% response rate with 90% confidence levels) in that setting. Whether significant durable benefit can be achieved with VBL therapy in patients whose tumor is sensitive in the HTSCA remains to be seen.
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PMID:Phase II study of vinblastine in advanced refractory ovarian carcinoma. 661 22

Ellipticine and some derivatives are highly cytotoxic substances which kill L1210 cells at concentrations ranging form 10(-8) to 10(-6)M. Some compounds in this series bind with high affinity to DNA (affinity constant between 10(7) M-1 and 10(5) M-1) by intercalation between base pairs. The antitumoral properties of these derivatives are thought to be related to their DNA-binding ability. Both 9-hydroxylation of ellipticine and quaternarization of 2-pyridinic nitrogen tend to increase DNA binding and antitumor activity. 2-Methyl-9-hydroxyellipticine (NSC 264-137) was selected for a phase I and later for a phase II trial in human cancer. This drug does not affect blood cell counts in animals or in man. It is not mutagenic in the Ames' test nor teratogenic in mice, but is endowed with anti-inflammatory properties and induces a marked decrease of motoricity in mice. Transient bradycardia and decrease of blood pressure are the most noticeable cardiovascular effects in dogs. This compound administered at 80-100 mg/m2/week in 1-h intravenous (IV) infusion induces objective remissions in about 25% of patients suffering from advanced breast cancer refractory to all other treatment. These remissions, which occurred after 3-4 weeks, lasted for 1-18 months. This drug seems particularly to improve the condition of patients suffering from oesteolytic breast cancer metastasis. Activity against anaplastic thyroid carcinoma and ovarian carcinoma has also been observed in some cases. Toxic side effects are nausea and vomiting (one-third of the patients), hypertension (less than 10% of the patients), muscular cramp (one-third of the patients), fatigue which can be very pronounced (in most patients after 3 months of treatment), mouth dryness, and mycosis of the tongue and esophagus (less than 20% of the patients).
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PMID:Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137). 700 58

Thirty-eight women with epithelial ovarian cancer were treated with gemcitabine, a new antimetabolite. All had previously received platinum, and 27 had also received paclitaxel. Four patients had a partial response giving a response rate of 13% in assessable patients (n = 31) and 11% for all patients entered. Additionally, 6 patients had stable disease with >50% reduction in CA-125 for at least 3 months. Activity was seen in patients resistant to both platinum and paclitaxel. Gemcitabine was well tolerated, with uncomplicated neutropenia the main hematological toxicity. Nonhematological toxicities were generally mild and included fatigue, myalgias, and skin rash. Gemcitabine has some activity in heavily pretreated ovarian cancer patients and deserves further investigation in this malignancy.
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PMID:Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel. 889 75

Thirty-six patients with advanced epithelial ovarian cancer received epirubicin as second-line therapy after primary treatment with carboplatin and cyclophosphamide. Thirty-four patients were evaluatable for response, 36 for toxicity. There were 9 responses (response rate 26.4%, 95% CI = 12.9-44.4), 2 complete and 7 partial. Median duration of response was 149 days (range 42-183); 4 patients with partial remission are still on study. Toxicity consisted of fatal cardiac failure and paravenous injection (1 patient), fatal leukopenia and sepsis (1 patient), and severe loss of appetite, nausea and vomiting, fatigue, and general malaise in 3 patients. Platelet nadir grade 4 (WHO) was observed in 2 patients while leukocyte nadir grade 4 was seen in 3 patients. The present study showed a high response rate from standard-dose epirubicin. Toxicity was acceptable in most patients, but 2 patients died from treatment complications which gives a treatment-related mortality rate of 6%. Response was primarily seen in patients with minor tumor load and in good general condition.
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PMID:A phase 2 study with epirubicin as second-line treatment of patients with advanced epithelial ovarian cancer. 891 Jun 29


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