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)

Purpose. To define the maximally tolerated dose (MTD) of ifosfamide when given with G-CSF on an every other week schedule, and to define the MTD of edatrexate that can be given every two weeks with an intense schedule of ifosfamide.Patients and Methods. Forty-one patients with metastatic or unresectable, locally advanced sarcoma participated in this 2-step phase I trial.The starting dose of ifosfamide was 10 gm/m(2) given by continuous intravenous infusion over 4 days every 2 weeks.When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m(2) intravenously every 2 weeks was added in subsequent cohorts of patients.Results. Myelosuppression was the most prominent toxicity. Fatigue, nausea, and vomiting were observed in the majority of patients. Ifosfamide 12 gm/m(2) given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m(2) could be given safety as an intravenous bolus with ifosfamide 10 gm/m(2) every 2 weeks. Therapeutic responses were observed in patients with measurable disease.Conclusions. This study demonstrates the feasibility of administering a dose-intense schedule of ifosfamide alone or ifosfamide with edatrexate that might be applied in the adjuvant or neo-adjuvant setting.
Sarcoma 1999
PMID:Evaluation of dose-intense Ifosfamide, with and without edatrexate, in adults with sarcoma. 1852 Dec 74

We describe a patient who underwent thoracic radiation therapy for biopsy-proven pulmonary spindle cell sarcoma in the left lower lobe, 15 months after birth. At the age of 37 she developed shoulder pain, fatigue, and progressive exertion dyspnoea. Chest X-ray revealed a pulmonary mass in the left lower lobe due to a cytology-proven malignant tumour.The patient underwent left pneumonectomy. Histology revealed a myosarcoma of the lung, similar to the previous sarcoma. Furthermore, the patient was diagnosed to have Turner syndrome mosaic and chromosomal analysis revealed a translocation t(1;13) in 3/50 metaphases. However a germline mutation of the p53 tumour suppressor gene was excluded. After 2 years of follow-up the patient is stable and there are no signs of recurrence of the tumour.We conclude a re-occurrence of this very rare malignant disorder of the lung after a 36-year interval in a patient with Turner syndrome mosaic. Following initial curative radiation therapy, with a remission over 36 years, lung resection was now successfully performed.
Sarcoma 2002
PMID:Successful resection of a re-occurred pulmonary myosarcoma in a patient with turner syndrome mosaic. 1852 51

This non-randomised Phase-I-study determined recommended dose (RD) and dose-limiting toxicities (DLTs) of four different schedules combining pemetrexed (P), gemcitabine (G) and cisplatin (C). Patients 18 years with locally advanced/metastatic cancer were enrolled. Doses were escalated for one 21-d (q3w; PGC d1, G d8) and three 28-d schedules (q4wA: PG d1, GC d15; q4wB: GC d1, PC d15; q4wC: PGC d1+15). Starting doses were P 400/500 mg/m(2) (q3w/q4w), G 800 mg/m(2) and C 40 mg/m(2). Sixty patients were enroled (n=12/14/30/4 for q3w/q4wA/q4wB/q4wC). Common cancers included head and neck (n=19), prostate (n=7), sarcoma (n=5) and stomach (n=5). Thirteen patients experienced DLTs, most frequently fatigue (n=4) and neutropenia (n=3). Schedule q4wB reached the highest doses (P 600 mg/m(2) d15; G 1250 mg/m(2) d1; C 70 mg/m(2)d1+15). There were no CRs, 11 PRs and 25 SDs (n=47). The PGC-combination was feasible. The recommended schedule for subsequent studies would be 1250 mg/m(2) G and 60 mg/m(2) C on d1, followed by 500 mg/m(2) P and 60 mg/m(2) C on d15.
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PMID:Phase-I-study of four different schedules of pemetrexed, gemcitabine and cisplatin in patients with locally advanced or metastatic solid tumours. 1880 96

The combination of trabectedin (T) and doxorubicin (D) was brought into clinical development in soft tissue sarcoma (STS) and advanced breast cancer (ABC) because of its in vitro and in vivo additive anti-tumour effect, the fact that there are no overlapping toxicities and the anti-tumour activity of T in those tumours. Feasibility and anti-tumour activity of T+D administered every 3 weeks were evaluated in 38 patients (STS=29, ABC=9) untreated for advanced disease. D was given at 60 mg/m(2) and T at escalating doses from 600 to 800 microg/m(2), which was the maximum tolerated dose due to dose-limiting febrile neutropenia and asthenia. The recommended dose--given to 18 patients in total--was 700 microg/m(2) T with 60 mg/m(2) D. The pharmacokinetic profile of T and D at cycle 1 was analysed in 20 patients. The most common toxicities included a severe but reversible ASAT/ALAT increase (94%), nausea/vomiting, neutropenia, asthenia/fatigue, stomatitis. Partial response and stable disease were assessed in 18% and 56% of STS patients and in 55% and 33% of ABC patients. No pharmacokinetic interaction between T and D was observed. The lack of cumulative toxicity and related complications and the promising activity in STS support further development of T+D.
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PMID:Phase I clinical and pharmacokinetic study of trabectedin and doxorubicin in advanced soft tissue sarcoma and breast cancer. 1911

Doxorubicin and ifosfamide are currently considered the cornerstones of treatment for advanced soft tissue sarcomas (STSs). Pegylated liposomal doxorubicin (PLD) has been shown to have equivalent activity to doxorubicin and an improved toxicity profile. A review of the medical records of 11 patients with a variety of STSs treated with PLD was performed. The median age of the patients was 54.8 years. Of the 11 patients, seven received no earlier systemic therapy for their sarcoma. The initial dose per course was 40-60 mg/m2 every 4 weeks with dose reduction to 40 mg/m2 in the second or third cycle. A median of 11 cycles was given (range, two to 29 cycles). Treatment was generally well tolerated. We did observe some toxic effects as described earlier with PLD, including mild myelosuppression, skin toxicity and fatigue. No cardiotoxicity was observed. Of the 11 treated patients, six had a partial response, two had a best response of stable disease and three had progressive disease. All six patients with a partial response had an extended time to progression. To date, two patients continue on treatment (15 and seven cycles); one patient has stable disease 60 months after withdrawal of PLD (after eight cycles) and one patient had progression of disease 7 months after the withdrawal of therapy after 20 cycles. Of the two patients with stabilization of their disease, one had progression after 29 months and one continues on treatment for 6 months. PLD is active and safe for long-term treatment of metastatic STSs and may be important in maintaining response.
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PMID:Long-term response to pegylated liposomal doxorubicin in patients with metastatic soft tissue sarcomas. 1934 97

PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR(12 weeks)). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR(12 weeks), five [26%] of19). PFR(12 weeks) was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.
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PMID:Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). 1945 27

The patient was 70-year-old man. He had complained of general fatigue and hoarseness for 5 months. Chest computed tomography scan demonstrated a large anterior mediastinal tumor. The diagnosis of high grade malignant sarcoma was established with needle biopsy and the complete resection through median sternotomy was conducted. The tumor was histopathologically diagnosed pleomorphic liposarcoma. Six months after operation, right supraclavicular lymph node metastasis was noted. Radiotherapy was performed, but the liver metastasis appeared subsequently 16 months after operation. Pleomorphic type is considered one of the poorest prognostic liposarcoma and should be required special attention.
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PMID:[Pleomorphic liposarcoma in anterior mediastium]. 2014 Oct 74

Radiation therapy is recommended as an adjuvant to resection for intermediate- and high-grade soft-tissue sarcomas; its role in bone sarcomas is largely limited to select patients with Ewing sarcoma. Despite the integral role of radiation therapy in soft-tissue sarcoma management, its optimal timing--preoperative versus postoperative--is uncertain, with each timing scenario having advantages and disadvantages. Preparation for radiation therapy involves a detailed planning session to optimize and standardize patient positioning and determine the target volume. Side effects of radiation therapy may include skin changes, delayed wound healing and other wound complications, fatigue, reduced range of motion of the affected limb, pain, and bone fractures.
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PMID:Use of radiation therapy for patients with soft-tissue and bone sarcomas. 2017 85

Pazopanib is an oral, multi-targeted, tyrosine kinase inhibitor (TKI) that binds to the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and several other key proteins responsible for angiogenesis, tumor growth and cell survival. Pazopanib exhibited in vivo and in vitro activity against tumor growth and, in early clinical trials, was well tolerated with the main side effects being hypertension, fatigue and gastrointestinal disorders. Pazopanib showed clinical activity in several tumors including renal cell cancer (RCC), breast cancer, soft tissue sarcoma, thyroid cancer, hepatocellular cancer and cervical cancer. A phase III clinical trial in metastatic RCC patients showed a significant improvement in progression-free survival, leading to its approval in the US. In metastatic breast cancer, the combination of pazopanib with lapatinib was more effective than lapatinib alone. At the time of the current publication, pazopanib is being evaluated in more than 35 phase II and III trials.
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PMID:Pazopanib: Clinical development of a potent anti-angiogenic drug. 2045 72

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger than 15 years. According to the World Health Organization, there are embryonal, alveolar and pleomorphic types of RMS. Most RMS patients present with a tumor mass in the head and neck region, urogenital tract or lower extremities. Unusual clinical presentation of the disease with massive bone marrow infiltration at the disease onset and mimicking hematologic neoplasm is rarely seen. A case is presented of a 14-year-old, previously healthy girl hospitalized for outpatiently detected leukocyte elevation. For the last two weeks, she had complained of fatigue, myalgia and frequent bruising. On admission, clinical examination revealed numerous petechiae and hematomas, enlarged left inguinal lymph node and palpable spleen 2 cm below left costal arch. Laboratory findings showed leukocytosis, anemia and thrombocytopenia. Bone marrow fine needle aspiration (FNA) produced a hypercellular bone marrow sample with suppression of all three hemocytopoiesis lines and bone marrow infiltration with numerous undifferentiated tumor cells. Considering the morphological, cytochemical and phenotypic characteristics, the cytologic diagnosis was: bone marrow infiltration with RMS cells. Abdominal computerized tomography revealed a primary tumor occupying the entire retropeoritoneal space. Tumor biopsy confirmed alveolar subtype of RMS. In conclusion, in cases of bone marrow infiltration with primitive, immature cells, RMS should be considered as differential diagnostic possibility. Adjuvant technologies (cytochemistry, immunocytochemistry, cytogenetic analysis, flow cytometry, and molecular analysis) can be very helpful in diagnostic work-up, and may lead to definitive diagnosis in some cases.
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PMID:Rhabdomyosarcoma with bone marrow infiltration mimicking hematologic neoplasia. 2069 43


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