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

Twenty four patients with advanced renal cell carcinoma were treated in a phase II trial with amonafide 300-450 mg/m2/day on days 1-5 every 21 days. There were no responders, 6 patients had stable disease, 14 experienced progressive disease and 4 were assumed to be non-responders as no evaluation was performed. There were no fatal toxicities although 8 patients had grade 3 or 4 granulocytopenia, 1 patient had grade 4 thrombocytopenia. Other toxicities included grade 3 diarrhea in 1 patient, grade 3 myopathy in 1 patient, severe nausea and vomiting in 1 patient and a facial rash, possibly a hypersensitivity reaction, in 1 patient. The median survival is 7.5 months. At this dosage and schedule, there is no evidence that amonafide has meaningful anti-tumor activity in patients with advanced renal cell carcinoma.
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PMID:Phase II evaluation of amonafide in renal cell carcinoma. A Southwest Oncology Group study. 180 14

FK973 is a novel, substituted dihydrobenzoxazine structurally similar to mitomycin. FK973 lacks cross-resistance with mitomycin, doxorubicin, and vincristine in murine tumor models. A phase I study of FK973 was initiated using a 30-minute infusion repeated every 4 weeks. Of 17 patients enrolled on the study, a minimum of three patients were entered at each dose level: 7, 14, 21, 30, and 45 mg/m2. The dose-limiting toxicity was a vascular leak syndrome (VLS) characterized by pericardial and pleural effusions, ascites, and subcutaneous edema. These conditions were observed in two patients treated with a dose of 30 mg/m2 and in four who received 45 mg/m2. VLS was observed 2 weeks after the third dose of 30 mg/m2 and one week after the second dose of 45 mg/m2. Of nine patients treated with a cumulative dose greater than 60 mg/m2, five experienced this toxic reaction. Reversible drug-related pneumonitis was noted in one patient after the third course of 30 mg/m2. Moderate nausea and vomiting were initially observed at a dose of 14 mg/m2 and alopecia at 30 mg/m2. Grade 3-4 granulocytopenia was observed in two patients treated with 45 mg/m2. Extensive myocardial degeneration was observed at autopsy in a patient who had received three courses of 30 mg/m2. One patient with metastatic colon carcinoma and another with metastatic pancreatic carcinoma experienced partial clinical responses. Although the drug's clinical activity appears promising, additional investigation is needed into the mechanism of toxicity prior to further clinical development.
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PMID:Phase I trial of FK973: description of a delayed vascular leak syndrome. 180 17

The effectiveness and side effects of a newly developed, repeatable depot-bromocriptine preparation, (Parlodel LAR, depot-bromocriptine), were studied in 7 acromegalic patients. A dose of 100 mg was injected at intervals of 28 days for 4 months, followed by 200 mg for 2 months. GH profiles (14 h) and an oral glucose load (oGTT) were performed prior to each injection. Depot-bromocriptine suppressed the mean serum profile GH concentration to less than 50% of the pretreatment value in 3 out of 7 patients (responders). Normalization of GH secretion was not achieved. During oGTT the mean serum GH concentration declined to 73%, 19% and 56% of the pretreatment value in the three responders (while on depot-bromocriptine 200 mg). IGF-I was reduced to 84% and 65% with 200 mg depot-bromocriptine in 2 GH responders only. No tumour shrinkage was observed in 3 patients with a visible tumor mass in NMR tomography. Side effects consisted of pronounced orthostatic dysregulation, nausea and vomiting on the day of injection in 3/7 patients. These results are comparable to the reported effectiveness and side effects of oral bromocriptine therapy. Depot-bromocriptine may be useful in selected responsive patients, particularly when compliance during oral therapy is a problem.
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PMID:Evaluation of a repeatable depot-bromocriptine preparation(Parlodel LAR) for the treatment of acromegaly. 180 12

Trimetrexate (TMTX), a potent inhibitor of the enzyme dihydrofolate reductase, was shown to be more active than its analogue, Methotrexate, against murine and human tumor cell lines in vitro and in vivo. We conducted two sequential phase I studies using a single bolus injection of TMTX every 14 days (Schedule A) and a weekly x 3 schedule every 4-6 weeks (Schedule B). Twenty-seven patients were treated on Schedule A with a TMTX dose range of 5 mg/m2 to 450 mg/m2 and 23 patients were treated on Schedule B with a TMTX dose range of 50 mg/m2 to 200 mg/m2. The dose limiting toxicity was myelosuppression on both schedules. The development of hematological toxicity was highly variable at different dose levels and within the same patient at a particular dose level. The nadir of blood counts was reached by Day 8 to 10 on the single dose schedule with recovery by Day 14. On Schedule B, the nadir granulocyte count occurred on Day 14 while platelet count was generally lowest by Day 20; the blood counts usually recovered 7 to 10 days after the last dose. Other common side-effects includes skin toxicity and stomatitis which were worse on the weekly schedule. Less common toxicities included mild nausea and vomiting, diarrhea, and transient deterioration in renal and hepatic functions. The occurrence of toxicity was not related to the extent of prior treatment, liver metastases, or accumulation of third space fluids. Based on our results, we recommend a starting TMTX dose for Phase II studies of 200 mg/m2 every 2 weeks or 100 mg/m2 to 125 mg/m2 on the weekly schedule.
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PMID:Phase I studies of trimetrexate using single and weekly dose schedules. 183 42

Conventional chemotherapy for unresectable or metastatic adenocarcinoma of the pancreas has had little effect on palliation or survival. Almost all studies of systemic therapy have involved empiric use of a variety of Phase II or conventional agents alone or in combination. On the basis of recent studies using a human tumor pancreatic cancer (PC) xenograft in nude mice, a Phase I clinical trial of cisplatin, high-dose cytosine arabinoside (Ara-C), and caffeine (CAC) was performed in patients with advanced incurable PC. A tolerable dose and schedule of the three agents were developed. Seven of 18 patients with measurable disease in this Phase I trial had partial responses to CAC. A Phase III comparison of CAC versus standard treatment using streptozotocin, mitomycin, and 5-fluorouracil (SMF) was performed. Eighty-two patients with advanced PC were entered into this random assignment trial. The two treatment arms were well balanced for the usual prognostic factors. Although the acute (e.g., nausea and vomiting) toxicities of CAC were greater than those of SMF, both groups of patients tolerated treatment resonably well. Ninety percent of patients were evaluable for response. Two patients (5.5%) on the CAC treatment arm (95% confidence interval [CI], 0% to 15%) and four patients (10.2%) on the SMF treatment arm (95% CI, 1% to 22%) had objective responses (partial response in measurable disease or improvement in evaluable disease). No complete remissions were observed. The 95% confidence limits of response for CAC and SMF overlapped. The median duration of survival for all patients on the SMF treatment arm was 10 months, although it was 5 months on the CAC treatment arm (P = 0.008). In this Phase III comparison, CAC was not superior to conventional therapy with SMF in terms of response and was inferior for survival. Neither regimen is effective treatment for advanced PC.
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PMID:A phase III comparison trial of streptozotocin, mitomycin, and 5-fluorouracil with cisplatin, cytosine arabinoside, and caffeine in patients with advanced pancreatic carcinoma. 183 42

Nine (eight males, one female) patients with unresectable liver tumor (seven HCC and two metastasis) were treated by two-routes chemotherapy using cis-diamminedichloroplatinum (CDDP) and sodium thiosulfate (STS). In these patients, 50-100 mg/body of CDDP was administered through the proper hepatic artery or right hepatic artery by one shot infusion or the balloon-occluded arterial infusion (BOAI) at 10 mg/min, and during administration, intra-inferior vena cava injection of STS (4 g/body) was given. None of 9 patients suffered nausea and vomiting during the treatment, 3 of 9 patients suffered nausea and vomiting to a mild degree after the treatment, none of 9 patients showed significant side effects, such as bone marrow suppression and/or renal disfunction. In conclusion, this study demonstrated the protection effect of STS injected in inferior vena cava against the toxicity of CDDP were well indicated.
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PMID:[Two routes chemotherapy by CDDP and STS against liver tumor]. 184 84

Thirty patients with histologically confirmed posterior fossa ependymomas operated on between January 1976 and December 1988 were reviewed. The median age was 44 years (range, 1-69 yr). There were 7 children (aged 5 yr or younger) and 23 adults (aged 16 yr or older). There were 18 female patients and 12 male patients. Headache, nausea and vomiting, and disequilibrium were the most frequent symptoms. The most common findings were ataxia and nystagmus. Gross total resection was performed in 8 patients (27%), subtotal resection in 21 patients (70%), and biopsy in only 1 patient (3%). Tumors were low grade in 73% and high grade in 27%. Twenty-seven patients underwent posterior fossa radiotherapy (median dose, 5400 cGy). Fourteen patients also underwent spinal irradiation (median dose, 3520 cGy). Age was the only significant prognostic factor identified (P less than 0.01). The 5-year survival rates were 76% for adults and 14% for children. All 14 patients who died had recurrent or residual tumor at the primary site. This review suggests that in patients with primary posterior fossa ependymomas the following is true: 1) the young patient (5 yr old or younger) has a poor prognosis; 2) there was a trend toward a better 5-year survival rate with a gross total resection; 3) if recurrence occurs, it will be at the primary intracranial site; and 4) symptomatic spinal seeding does not occur frequently.
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PMID:Posterior fossa ependymomas: report of 30 cases and review of the literature. 187 43

The effects of intra-arterial infusion of degradable starch microsphere (DSM) on hepatic hemodynamics were studied in 22 patients with metastatic liver cancer and the clinical outcome with mitomycin C (MMC) combined with DSM was reported herein. Hepatic arterial blood flow, measured with a transit-time ultrasonic blood flow meter, changed 283 +/- 27 ml/min to 40 +/- 36 ml/min by an hepatic arterial infusion of DSM and, a mean occlusion time aS 24 +/- 11 min. Combined infusion with DSM and MMC reduced MMC levels in the peripheral blood at 0.0248 less than p less than 0.0421, compared with those by an infusion with MMC alone and consequently, these findings proved to result from intrahepatic accumulation of MMC. RI-angiography using 99mTc-macroaggregated albumin (99mTc-MAA) was performed to examine hemodynamic changes in the metastatic liver and, a tumor (T) to non-tumor (N) ratio of 99mTc-MAA accumulation increased 0.37 to 0.62 by combined use of DSM. Thus, an intra-arterial infusion combined DSM and MCC was performed for 22 patients with unresectable hepatic metastases. Tumor regression was observed in 16 patients (73%). Side effects possibly attributable to DSM was transient nausea and vomiting. These results show that combined use of DSM is effective for intra-arterial chemotherapy against metastatic hepatic cancer.
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PMID:[Targeting cancer chemotherapy for metastatic liver cancer--effects of DSM on hepatic hemodynamics and on clinical outcome]. 190 32

Imipenem/cilastatin sodium (IPM/CS), which has a broad spectrum of activity against both Gram-positive and -negative bacteria including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, was used as the second choice for severe infections associated with hematological disorders. Sixty-five patients were treated with IPM/CS. Among them, 53 patients were evaluable for the clinical efficacy. Twelve patients were not evaluable due to the following reasons: 5 patients were treated with combinations of other regimens such as cefzonam, cefmenoxime, ciprofloxacin or gamma-globulin, 5 were patients to whom IPM/CS was administered as the first choice, and the remaining 2 patients were thought to be suffering not from febrile infections but from febrile tumor. Excellent responses were observed in 10 (18.9%) patients and good responses in 23 (43.4%) patients, with an overall rate of efficacy of 62.3%. The efficacy in septic patients was 75% (3/4), and that in patients whose peripheral granulocytes were continuously below 100/microliter was also 75% (6/8). Two patients who suffered from tumor fever and 5 patients who had received no chemotherapy before IPM/CS administration were included in the final evaluation of side effects. Side effects were observed in 16 patients (16/60, 26.7%). In a 61 years, female patient, a skin eruption was found 4 days after IPM/CS therapy was started. In 15 patients, mild gastrointestinal symptoms such as nausea and vomiting were identified within a few days after IPM/CS treatment was started. Abnormal laboratory data such as eosinophilia, liver dysfunction or renal dysfunction were also identified in 4 patients (4/60, 6.7%). Degrees of these abnormalities were very slight, however, and the continuation of treatment was not disturbed. These results indicated that IPM/CS was an effective second line regimen of chemotherapy for the treatment of severe infections in patients with hematological disorders.
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PMID:[Clinical evaluation of imipenem/cilastatin sodium as a second line regimen in severe infections associated with hematologic disorders]. 192 Aug 14

Didemnin B is a depsipeptide extracted from the marine tunicate Trididemnin cyanophorum. This agent is a potent inhibitor of L1210 growth in vitro and has activity against murine B16 melanoma, P388 leukemia, and M5076 sarcoma in vivo. The results of preclinical toxicologic tests demonstrated abnormalities in clotting parameters thought to be secondary to drug-induced liver dysfunction. Thirty-five patients with advanced cancer received didemnin B according to a 5-day bolus schedule with dose levels ranging from 0.03 to 2.00 mg/m2/d. The dose-limiting toxicity was nausea and vomiting. Sporadic elevation of the hepatic enzyme level occurred but was not dose limiting. Two patients had anaphylactic symptoms possibly related to the 5% polyoxyethylated castor oil (Cremophor EL, BASF, Ludwigshafen, Germany) vehicle during the drug infusion. Clinical bleeding was not observed and myelosuppression was not significant. No partial or complete tumor responses were seen. The recommended Phase II dose for the 5-day schedule is 1.6 mg/m2/d.
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PMID:A phase I clinical trial of didemnin B. 193 1


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