Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a patient who developed multifocal cerebral demyelination with the use of 5-fluorouracil, levamisole, and leucovorin as adjuvant treatment for intestinal adenocarcinoma. The clinical features were acute confusion, restlessness, ataxia, and slurred speech. Magnetic resonance imaging revealed multifocal enhancing white matter lesions. Brain biopsy showed a well-demarcated area of demyelination in cerebral white matter. The patient improved clinically and radiologically after cessation of chemotherapy and a short course of steroids. There have been only 4 previously reported cases of multifocal leukoencephalopathy related to the use of combination 5-fluorouracil and levamisole. The extensive use of these agents as adjuvant treatment for colorectal carcinoma may result in more frequent recognition of this form of neurological toxicity.
Cancer Invest 1994
PMID:Cerebral demyelination with 5-fluorouracil and levamisole. 803 57

Bone marrow transplantation (BMT) has evolved over the last decade from a controversial research procedure to a standard therapeutic modality, becoming an important innovative treatment for hematological malignancies, solid tumors, immunodeficiency diseases and metabolic disorders. Historically in research and clinical literature, the BMT procedure is divided into several stages, each accompanied by particular emotional tones and psychological issues. In providing care for transplant recipients, donors, and families, caregivers must be familiar with the psychological stages of the procedure, the psychological themes such as body image, and the patient's mechanisms of coping with the stress of such protocols. BMT's complex regimens of high-dose chemotherapy and total-body irradiation, germ-free environments, graft-versus-host disease, and total parenteral nutrition can precipitate significant psychological sequelae in some patients with acute and long-term consequences. In response to their illness, transplant patients may also develop emotional disturbances of anxiety, depression, agitation, and non-compliance. This paper will address the psychological care of the patient, donor and family from pre-BMT consultation, through informed consent, hospitalization and convalescence. Various psychotherapeutic, pharmacological and behavioral interventions will be briefly described. Finally, areas of research in quality of life after BMT and factors that may predict BMT adjustment and outcome will be explored. We hope this brief paper will familiarize the reader with this psychologically intriguing field and will provide a departure point for future reading, study, research, and patient/family care.
Support Care Cancer 1994 Jan
PMID:Bone marrow transplantation: support of the patient and his/her family. 815 56

A structured, prospective telephone interview was used to assess the prevalence of akathisia in 24 cancer patients receiving metoclopramide or prochlorperazine during or after chemotherapy. Half of the patients reported subjective motor restlessness, and 75% stated that they would not have informed staff. This report suggests that akathisia is frequently unrecognized in chemotherapy patients receiving metoclopramide and prochlorperazine.
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PMID:Antiemetic-induced akathisia in cancer patients receiving chemotherapy. 775 44

In a partially blinded randomised cross-over trial, 78 patients receiving cisplatinum based chemotherapy were assigned to receive two forms of antiemetic therapy: SAD, a regimen composed of serenace (haloperidol), ativan (lorazepam), and dexamethasone followed by low dose maxolon (metoclopramide) and STADMAX, a regimen composed of scopolamine (hyoscine), tavegyl (clemastine), ativan, dexamethasone and high dose maxolon. Each antiemetic regimen was given in random order, with the first and second cycles of cytotoxic chemotherapy. 66 (85%) patients completed both cycles of antiemetic therapy and were available for the cross-over comparison. Significantly less acute vomiting, as assessed by nurse observer (P < 0.0001), and less delayed vomiting, as assessed by patient diary (P = 0.03), were seen with STADMAX. In the first 18 h, complete control of vomiting (no episodes) was achieved in 30 (45%) patients with STADMAX compared with 10 (15%) receiving SAD. Overall, major control of emesis (< or = 2 episodes) was achieved in 56 (85%) patients with STADMAX compared with 35 (53%) receiving SAD. Vomiting was also better controlled on STADMAX in the week after this initial 18 hour period based on the 7 day patient diary with no vomiting episodes in 18/65 (28%) on STADMAX vs. 13/65 (20%) on SAD. However, no significant differences in appetite, nausea or vomiting were found when based on linear analogue self assessment (LASA) scales recorded by patients. Significant differences in side effects of the two antiemetic regimens were noted on LASA scales with more dry mouth (P = 0.01), blurred vision (P = 0.03) and diarrhoea (P = 0.04) associated with STADMAX and more restlessness (P = 0.002) associated with SAD. Significantly, no episodes of dystonic reactions were seen among patients on either regimen. In the 68 patients who completed both cycles and were in a position to express a preference, 46 (68%) preferred STADMAX compared with only 20 (29%) who preferred SAD (P = 0.001), while 2 patients expressed no preference. It is concluded that STADMAX is the preferred regimen to SAD for the control of cisplatinum-related emesis. It has a role, both where specific serotonin 3 antagonists are not available and as a model for building more effective combinations where these agents are available.
Eur J Cancer 1993
PMID:A randomised cross-over trial of antiemetic therapy for platinum-based chemotherapy. Improved control with an intensive multiagent regimen. 839 24

Doxorubicin (DOX) efflux in drug-resistant cells is blocked by phenothiazines such as trifluoperazine (TFP) and prochlorperazine (PCZ) in vitro. The present phase I study was conducted in 13 patients with advanced, incurable, nonhematologic tumors to determine whether PCZ plasma levels high enough to block DOX efflux could be achieved in vivo. The treatment schedule consisted of prehydration and i.v. administration of 15, 30, 50, and 75 mg/m2 PCZ followed by a standard dose of 60 mg/m2 DOX. The hematologic toxicities attributable to DOX were as expected and independent of the PCZ dose used. Toxicities attributable to PCZ were sedation, dryness of the mouth, cramps, chills, and restlessness. The maximal tolerated dose (MTD) of PCZ in this schedule was 75 mg/m2. Pharmacokinetic analysis indicated a large interpatient variation in peak plasma PCZ levels that ranged from 95 to 1100 ng/ml. The three plasma half-lives of PCZ were: t1/2 alpha (+/- SE), 20.9 +/- 5.3 min; t1/2 beta, 1.8 +/- 0.3 h; and t1/2 gamma, 21.9 +/- 5.3 h. The volume of distribution (Vd), total clearance (ClT), and area under the curve (AUC) for PCZ were 2254 +/- 886 l/m2, 60.2 +/- 13.5 l m-2 h-1, and 1624 +/- 686 ng ml-1 h, respectively. DOX retention in tumor cells retrieved from patients during the course of therapy indicated the appearance of cells with enhanced DOX retention. The combination of DOX and high-dose i.v. PCZ appeared to be safe, well tolerated, and active in non-small-cell lung carcinoma.
Cancer Chemother Pharmacol 1993
PMID:Prochlorperazine as a doxorubicin-efflux blocker: phase I clinical and pharmacokinetics studies. 845 81

In advanced cancer patients close to death, delirium, multifocal myoclonus, and restlessness may occur. Multi-organ failure and related metabolic changes are mostly responsible for these symptoms. A pharmacologic approach to manage the delirium is necessary in the majority of cases. Benzodiazepines, neuroleptics, and barbiturates are the most common drugs used. In the case reported, propofol administered at very low doses provided good control of neuropsychiatric symptoms. After a loading dose of 20 mg, an infusion of 50-70 mg per hr was started. The patient died peacefully after 8 hr of propofol infusion, without requiring opioids. Propofol seems to be a promising drug in treating the terminal agitated state that can be associated with the dying process.
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PMID:Propofol in terminal care. 859 25

The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous-infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.
Eur J Cancer 1995 Dec
PMID:A phase I/II evaluation of metoclopramide as a radiosensitiser in patients with inoperable squamous cell carcinoma of the lung. 865 42

SK&F107647 is a synthetic hematoregulatory peptide (HP) increases both the number and function of progenitor cells, enabling improved survival after lethal myelosuppression, lethal fungal infection, and lethal herpes simplex virus infection in murine models. This Phase I single-blind placebo-controlled dose-rising crossover trial examined the efficacy of SK&F107647 in patients who had incurable solid tumor malignancies. Sixteen patients were treated. Six adverse events in 3 patients were considered to be possibly related to SK& F107647; all were mild to moderate in nature (mild nervousness and agitation at 0.01 ng/kg, moderate fever and mild nausea at 0.1 ng/kg, elevated hepatic enzymes at 0.1 ng/kg, and mild vomiting at 1.0 ng/kg). Plasma half-life was 2.44 hours (+/-1.07 standard deviation). The observed area volume of distribution was 16.7 L (+/-7.7 standard deviation) and clearance was 5.04 L/hour (+/-1.83 standard deviation). When administered as a single 2-hour intravenous infusion at doses ranging from 0.01 to 100 ng/kg, SK&F107647 is safe and well tolerated.
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PMID:SK&F107647: a synthetic hematoregulatory peptide in patients with solid tumor malignancies: a phase I trial. 953 10

Restlessness can make dying unnecessarily difficult, not only for the patient himself, but also for his family and the physician in charge. Four cancer patients, three men aged 69, 80 and 66 and a woman aged 88, displayed severe terminal restlessness, caused by nicotine abstinence, hypoglycaemia, constipation and urinary retention, respectively. Suitable interventions helped the patients to die in peace and dignity. Facing restless terminal patients the physician should think of withdrawal symptoms, metabolic derangements, full bladder and (or) rectum and intoxication by drugs, frequently morphine. Interventions directed at those problems may bring surprising results.
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PMID:[Treatment of restlessness in dying patients: more than just sedation]. 975 32

The pyrazoloacridine (PZA) analogue NSC366140 (PD115934) entered clinical trial based on unique preclinical characteristics including solid tumor selectivity in vitro, marked antitumor activity in vivo against murine solid tumors, selectivity against noncycling cells, and activity against multidrug-resistant tumor cells. After identification of the pre-clinical efficacy and an acceptable toxicity profile, a Phase I study of PZA was carried out. A total of 28 patients was entered and received a total of 67 treatment courses. The drug was administered via a 1-h infusion every 21 days. The starting dose was 30 mg/m2 with 2-fold dose escalations through 480 mg/m2. The next dose escalation was 50%, to 720 mg/m2. Grade I through grade IV toxicities were observed. Since no dose-limiting toxicities were observed at 480 mg/m2, and up to grade IV toxicities were observed at 720 mg/m2, an intermediate dose, 600 mg/m2, was evaluated. Dose-limiting toxicities at 720 mg/m2 were hematological (grade III and IV neutropenia) in four of six patients and neurological (up to grade III cerebral toxicities, including restlessness, dizziness, agitation/anxiety, personality changes, and nightmares, as well as myoclonus) in three of six patients treated. The pharmacokinetic parameters which helped predict these toxicities included area under the curve and peak plasma level. Pharmacokinetic studies showed interpatient variations in all parameters studied. The mean area under the curve levels of PZA at the highest two dose levels in patients were near the level detected in mice at their maximum tolerated total dose. The recommended starting dose for Phase II trials using this schedule is 600 mg/m2.
Clin Cancer Res 1995 Dec
PMID:Phase I clinical trial of pyrazoloacridine NSC366140 (PD115934). 981 48


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