Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen patients who developed CT or MRI scan evidence of recurrent diffuse astrocytoma after radiation therapy and nitrosourea-containing chemotherapy received ifosfamide (2500 mg/m2/day for 3 consecutive days) and mesna (500 mg/m2/dose, 5 doses/day for 3 consecutive days). Toxicity consisted primarily of leukopenia in that 60 percent of patients developed leukocyte nadirs less than 1500/mcL. Excessive somnolence occurred in three patients and may have contributed to a case of fatal pneumonia in one patient but was reversible in the other two. No patient had CT or MRI scan evidence of tumor regression. One patient remains stable at 11.3 + months, but all other patients developed evidence of progressive disease less than 6 months from initiation of therapy. The median times to tumor progression and death were 2.0 and 4.8 months, respectively. In conclusion, while ifosfamide and mesna can be given safely at this dose and schedule, there is no evidence of antitumor effect. The degree of leukopenia observed likely would prevent further dose escalation of ifosfamide or addition of other myelosuppressive agents without additional means of bone marrow support in this population of patients.
 ...
PMID:Phase II study of ifosfamide with mesna in adult patients with recurrent diffuse astrocytoma. 190 6

A 72-year-old woman complaining of somnolence and thirst was diagnosed to have a hypercalcemic crisis (corrected serum calcium level, 17.4 mg/dl) associated with encephalopathy and nephropathy. Imaging diagnostic techniques demonstrated a retroperitoneal tumor at the median site of right renal pelvis. Hormonal studies revealed that plasma levels of thromboxane B2, prostaglandin (PG) E2, 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin F2 alpha (PGF2 alpha) were markedly elevated. The tumor was successfully removed by operation; her serum calcium level and PG levels normalized without any treatment indicating that this case belongs to the category of humoral hypercalcemia of malignancy (HHM). Pathologically, this tumor was diagnosed to be a benign neurilemoma. Parathyroid hormone-related protein (PTHrP) radioimmunoassay and Northern blot hybridization for PTHrP mRNA were negative. The current case demonstrates that hypercalcemic crisis could be induced by a curable benign neurilemoma, and suggests that this HHM-like morbidity was associated with markedly elevated plasma PG levels.
 ...
PMID:Retroperitoneal neurilemoma presenting with humoral hypercalcemia associated with markedly elevated plasma prostaglandin levels. 191 78

A Phase I/II accelerated fractionation study for high-grade cerebral astrocytomas began in October 1987. Forty-two patients, 25 men and 17 women, were entered in the study. Median age was 58.5 years of age (range, 32 to 78 years). Performance status was 0, 1, 2, and 3 on Eastern Cooperative Oncology Group (ECOG) scale for 13, 19, 9, and 1 patients, respectively. Thirty-six patients had undergone partial resection, and six had stereotactic biopsy only. All patients had histologically proven astrocytomas (6 Grade 3, and 36 Grade 4). Treatment consisted of radiation therapy doses of 4400 cGy in 22 daily fractions to the whole brain plus a boost of 1600 cGy in 8 fractions given concomitantly with the last 8 whole-brain treatments using a twice daily schedule with an interfraction interval of 8 hours. Median survival time was 57 weeks from the date of starting irradiation. Survival was 50% and 28% at 1 and 2 years, respectively. Alopecia and scalp erythema were seen in all patients; nine patients had localized areas of moist desquamation in the retroauricular region. Decreased hearing and serous otitis media were seen in five patients within 1 to 2 months from the end of treatment. Increasing somnolence was marked in eight patients with progressive deterioration of performance status; computerized axial tomography (CAT) scan studies in all eight patients showed evidence of disease recurrence with associated brain edema and mass effect. Three patients had a second resection for a recurrent tumor with no evidence of brain necrosis at craniotomy. To date, the accelerated fractionation schedule appears to be well tolerated with valuable shortening of overall treatment time. The preliminary results are encouraging, and longer follow-up time is required to evaluate tumor control and toxicity.
 ...
PMID:Accelerated fractionation for high-grade cerebral astrocytomas. Preliminary treatment results. 201 30

The new anticancer agent lonidamine has been recently revisited for the treatment of various solid tumors, due to its peculiar and unusual mechanism of action (ie, interference with energy metabolism of tumor cells, morphologically displayed by the appearance of "condensed mitochondria"). First generation trials have in fact demonstrated therapeutic activity and an unusual toxicity profile. Lonidamine is devoid of conventional side effects induced by antiproliferative agents (ie, myelosuppression, stomatitis, cystitis, alopecia, renal, hepatic, and cardiac toxicity). No serious or life-threatening adverse reactions have been recorded even over long term treatment periods. Given as a single agent (in daily doses ranging between 300 and 900 mg) lonidamine induces the following side effects: myalgia, testicular pain, asthenia, ototoxicity, nausea and vomiting, gastric pain, and drowsiness. Hyperesthesia and photophobia have also been reported. In combination with radiotherapy (in oral daily doses ranging between 300 and 450 mg) lonidamine was well tolerated, without any reported evidence of additional toxicity. When associated with cytotoxic agents no enhanced toxicity was observed. In particular, myelosuppression and other conventional nonhematological adverse reactions were never greater than would be expected with chemotherapy alone. The same applies to toxicity and tolerance of lonidamine when used concurrently with hypertermia. The data collected from large series of cancer patients treated with this new agent show that lonidamine is a safe drug whether used alone or in combination with other effective anticancer treatments. The reported therapeutic efficacy and the peculiar toxic profile make lonidamine an interesting new drug for future clinical trials.
 ...
PMID:Toxicity and clinical tolerance of lonidamine. 203 Nov 92

The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.
 ...
PMID:Fludarabine: a review. 206 37

From May 1986 until July 1987, oral morphine hydrochloride in water solution was used in terminal patients, under a strict protocol of administration, and complying with the basic principles of Palliative Care. A retrospective study was carried out on the 40 patients who had received the drug for more than three consecutive days. As shown in Table 1, the average age of the treated patients was 70 years. The ambulatory patients represented 27.5% of the sample. The average initial dose was 60 mg, and the average maintenance dose was 120 mg. The median treatment time was 45 days. "Good" results were achieved in 85% of the patients, and "fairly good" in the remainder ("good" results were defined as "satisfactory symptom control, good life quality"--in this group there were some patients who obtained total suppression of the symptoms and optimal life-quality, i.e. "excellent" results; "bad" results were defined as "total absence of therapeutic effect"; and "fairly good" results, the intermediate cases). The more frequently treated symptoms were: 67.5%, pain due to tumor mass; and 20%, pain due to nerve compression-invasion, bone pain, and dyspnoea due to pulmonary metastases or primary lung cancer: total symptoms was more than a hundred per cent, because a number of patients had more than one symptom. Whenever necessary, adjuvant drugs were employed. Side effects were seen in 37% of the patients (specially nausea, vomiting, constipation, and somnolence for more than four days).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Oral morphine in the treatment of patients with terminal disease]. 213 Feb 44

Two hundred one patients were entered in a single-dose phase I trial of WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid]. Major toxic effects included emesis and hypotension. The observed minor toxic effects were somnolence and sneezing. Two infusion schedules were tested: long-infusion time, which fixed the rate, but varied total time; and short-infusion time, which varied the rate, but fixed the time to 15 minutes. Emesis was significantly influenced by infusion time; the long schedule caused a 57% incidence whereas the short schedule caused only a 28% incidence. Within the long-infusion group, higher-dose patients and women were more likely to vomit. Although only 15% of the entire group had hypotension, the long-infusion schedule had a hypotension incidence of 23%; the short schedule had an incidence of only 3% (P less than 0.0005). Within the long-infusion group, dose and tumor site significantly influenced the incidence of hypotension. No factors were associated with these toxic effects in the short-infusion schedule. However, certain toxic effects were too infrequent to detect significant differences. For future trials we recommend 740 mg/m2 infused in 15 minutes. With this schedule, vomiting was seen in 25% of infusions and hypotension was seen in only one of 68 infusions. To date, no delayed toxic effects have been detected in any organ system, and the trial resulted in no toxic deaths.
 ...
PMID:Final report of the phase I trial of single-dose WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid]. 243 74

A 68-year-old male was hospitalized because of headache, nausea, and disturbance of consciousness. Neurological examination on admission disclosed somnolence, disorientation, marked neck stiffness, papilledema, and quadriparesis. Computed tomography (CT) scanning demonstrated a round mass with marked contrast enhancement in the right sylvian fissure and small contrast-enhanced masses in the interpeduncular, quadrigeminal and ambient cisterns. CT also showed marked peritumoral edema, a midline shift, and hydrocephalus. The patient's consciousness level and respiration deteriorated 3 days after admission and a craniotomy was performed. The tumor, which was well demarcated, firmly attached to the sphenoidal ridge, and grossly appeared to be a meningioma, was totally removed. Histologically, the tumor had two well defined components, glioblastoma and fibrosarcoma. The patient underwent ventriculoperitoneal shunting, chemotherapy, and radiotherapy after surgery, but the primary tumor soon recurred, with scalp metastasis, and he died 5 months postoperatively. Autopsy revealed metastases to the liver, spleen, and spinal cord. The histogenesis of this mixed tumor and the mechanism of extracranial metastasis are discussed, and the literature is reviewed.
 ...
PMID:[Gliosarcoma with multiple extracranial metastases. Case report]. 248 46

The development of the recombinant alpha interferons has provided a prototype for the clinical development of biological compounds. Over 5,000 patients have now been treated with alpha interferons, and from this experience, some general principles relating to the phase I-III testing of biologicals have emerged. Clinical trials of alpha interferon have suggested dose-response relationships and provided a clearer picture of schedule dependence. These trials have also indicated that the extent of tumor burden and identification of sensitive patient subtypes may be critical factors affecting the potential activity of biological compounds. Recent studies using interferon in the treatment of chronic viral hepatitis have also generated promising results, suggesting an even greater antiviral role for the drug. The toxicity profile of the alpha interferons is unusual. Fever and influenza-like symptoms occur in almost all patients at all doses and schedules, and are usually dose limiting. Somnolence and other generally mild CNS effects occur in a small percentage of patients. Hematologic toxicity occurs but is minimal at lower doses and is noncumulative and rapidly reversible at all doses. Gastrointestinal toxicity is mild. No other unusual or unexpected toxicities have been reported, and early reports of cardiovascular toxicity have not been confirmed in large trials. The full role of alpha interferon in antineoplastic and antiviral therapy will be resolved in the coming years. This review summarizes existing safety and efficacy data for the alpha interferons.
 ...
PMID:Alpha interferons: a clinical overview. 267 86

One hundred and one postmenopausal patients with advanced breast cancer were enrolled in a randomized phase II clinical trial to investigate the clinical and hormonal response to aminoglutethimide administered at daily doses of 2 x 125 mg, 3 x 125 mg or 2 x 250 mg, with no addition of hydrocortisone. Among 71 evaluable patients 25% showed objective tumor response (three complete, 15 partial), at all three dose levels and irrespective of the major tumor site. Previous treatment with Tamoxifen had been successful in 75%. Out of the 18 responding patients 10 had estrogen receptor positive, four had estrogen receptor negative tumors; the receptor status was unknown in four other patients. Progression-free interval was more than 700 days in 50% of the responders. Drowsiness caused early drug withdrawal in one patient. Side-effects were very mild, comparing favorably with standard therapy of 250 mg aminoglutethimide q.i.d. plus hydrocortisone. Plasma estrogen levels were reduced by all doses to the same 50% or less as in patients on standard treatment. In nine out of 27 patients a further decrease of estrone levels could be monitored with clinically improved results in five. Plasma cortisol and mineralocorticoids remained normal throughout more than 6 months. The original role of hydrocortisone administration to suppress a reflex rise of ATH in 'medical adrenalectomy' with standard dose aminoglutethimide is no longer tenable. Further phase III comparative clinical results pending, low dose aminoglutethimide as an aromatase inhibitor may at present be considered as an appropriate second-line endocrine treatment with low toxicity and expense.
 ...
PMID:Low dose aminoglutethimide without hydrocortisone for the treatment of advanced postmenopausal breast cancer. 270 89


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