1/12. Phase I evaluation of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase c-alpha, in patients with advanced cancer.PURPOSE: To determine the maximum-tolerated dose (MTD) and pharmacologic behavior of ISIS 3521 (ISI 641A), an antisense phosphorothioate oligonucleotide to protein kinase c-alpha. patients AND methods: Thirty-six patients with advanced cancer received 99 cycles of ISIS 3521 (0.15 to 6.0 mg/kg/d) as a 2-hour intravenous infusion administered three times per week for 3 consecutive weeks and repeated every 4 weeks. plasma and urine sampling was performed during the first week of treatment and subjected to capillary gel electrophoresis to determine full-length antisense oligonucleotide in addition to chain-shortened metabolites. RESULTS: Drug-related toxicities included mild to moderate nausea, vomiting, fever, chills, and fatigue. Hematologic toxicity was limited to thrombocytopenia (grade 1, four patients; grade 2, one patient; grade 3, one patient). There was no relationship between dose, maximum concentration of the drug (C(max)), or area under the plasma concentration versus time curve (AUC) and coagulation times or complement levels. Dose escalation was discontinued because of the attainment of peak plasma concentrations, which approached that associated with complement activation in primates. Two patients with non-Hodgkin's lymphoma who completed 17 and nine cycles of therapy achieved complete responses. The pharmacokinetic profile of ISIS 3521 revealed a short elimination half-life (18 to 92 minutes), as well as a dose-dependent decrease in clearance and dose-dependent increases in C(max), AUC, and elimination half-life. CONCLUSION: No dose-limiting toxicity of ISIS 3521 was identified, and clinical activity was observed. A short elimination half-life was identified, which suggests that alternate schedules with prolonged administration may be necessary for further clinical development.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/12. methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature.ifosfamide is an alkylating agent used in the treatment of a variety of solid tumours. Ten to 15% of patients treated with ifosfamide develop an encephalopathy. methylene blue (MB) may be used in the treatment of this encephalopathy. The purpose of this study was to evaluate the neuroprotective effect of MB in these patients and to review the literature. Between 1993 and 1997, 52 patients (age 16-77 years) with solid tumours were treated with ifosfamide in dosages ranging from 3 to 5 g m(-2) q3w when given in combination schedules and up to 12 g m(-2) q4w when given as a single agent. Twelve patients developed central nervous system (CNS) depression, defined as National Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicity grade 2 or higher. Eight were treated with MB at a dose of 6 x 50 mg day(-1) intravenously (i.v.). Four recovered fully within 24 h, two recovered partially after 24 h and completely after 48 h while two recovered only after 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 x 50 mg day(-1) i.v. for the subsequent chemotherapy cycles. Two developed milder encephalopathy; one had no CNS depression at all. We conclude that MB is an effective treatment for ifosfamide-induced encephalopathy. Our findings suggest that it may also be used as a prophylactic agent.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
3/12. Fatal liver failure after the administration of raltitrexed for cancer chemotherapy: a report of two cases.BACKGROUND: Acute fatal liver failure is a relatively rare event after the administration of antineoplastic drugs. To the authors' knowledge, there have been no published reports of this phenomenon after the administration of the widely applied cytotoxic agent raltitrexed. methods: The authors present two cases of fulminant fatal liver failure that occurred after the administration of raltitrexed as anticancer chemotherapy. RESULTS: A female patient age 76 years and a male patient age 56 years were given raltitrexed as adjuvant treatment of colorectal carcinoma and as palliative therapy for advanced biliary carcinoma, respectively. Although the initial cycles of chemotherapy were uneventful, both patients developed fulminant liver failure with rapid deterioration of their condition after the second and sixth cycles of chemotherapy, respectively, and both died within 24 hours despite immediate hospitalization. Histologic evaluation of liver samples taken during autopsy showed signs of acute necrosis involving roughly 50% of the liver without signs of subacute liver toxicity. CONCLUSIONS: To the authors' knowledge the current study is the first to demonstrate fatal liver toxicity after chemotherapy with the thymidylate synthase inhibitor raltitrexed. Clinicians should be aware of the potential acute fatal side effect of this otherwise well tolerated and widely used cytotoxic agent.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
4/12. hyperalgesia: an emerging iatrogenic syndrome.Clinical reports suggest that opioids, intended to abolish pain, can unexpectedly produce hyperalgesia. This paradoxical effect may be mechanistically related to tolerance induced by increasing doses of opioids. Two case reports illustrate a syndrome characterized by increasing pain pursued by escalating opioid doses, which results in a worsening of the clinical picture. Several experimental data may help explain the course of this challenging clinical condition. In escalating opioid doses rapidly, a risk of opioid-induced hyperalgesia should be recognized, as higher doses of opioids may stimulate rather than inhibit the central nervous system by different mechanisms. Alternative procedures should be taken into consideration to break this cycle, should it occur. More data are needed to detect this condition, as currently no diagnostic information on specific markers, clinical or biochemical, exists.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
5/12. A tumor in the medulla oblongata producing beta-HCG and AFP.A 23 year-old woman presented with dysarthria, hoarseness, dysphasia, ataxia and dyspnoea. MRI showed a mass of heterogeneous intensity at the dorsal medulla oblongata. Laboratory studies revealed high serum alpha-fetoprotein (AFP) and beta-subunit human chorionic gonadotropin (beta-HCG) levels. No other tumours were found on systemic investigation. An intracranial non-germinomatous germ cell tumour (NGGCT) was strongly suspected. The patient received combination chemotherapy using ifosfamide, cisplatin, and etoposide and local irradiation to a total of 52 Gy. serum AFP and beta-HCG levels normalized after four cycles of chemotherapy and she became asymptomatic apart from mild postural hypotension. A follow-up MRI showed only a tiny residual lesion in the medulla oblongata, which has been stable for more than three years. Surgical resection should be carefully considered in patients with brainstem tumours with elevation of serum tumour markers as chemo- and radiotherapy may be effective for brainstem NGGCT.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
6/12. Placental site trophoblastic tumor in a postmenopausal woman.Placental site trophoblastic tumor is a rare neoplasm that arises in the trophoblastic tissue of the placental bed. This case report is unusual because of the patient's advanced age at the time of diagnosis and the favorable response of the disease to chemotherapy. Although the clinical course is benign for most patients with placental site trophoblastic tumor, the malignant variant of the disease is characterized by recurrence, relative insensitivity to radiation and chemotherapy, and death. To the authors' knowledge, the 53-year-old woman reported is the oldest patient with histologically confirmed placental site trophoblastic tumor. Initially, surgery, radiation, and multiagent chemotherapy failed to control vaginal and pulmonary metastatic disease. After administration of four treatment cycles of a "second-line" chemotherapeutic regimen consisting of cyclophosphamide and cisplatin, complete clinical and radiologic remission was achieved. The patient's serum level of human chorionic gonadotropin has remained undetectable, and she has been without measurable evidence of disease for 16 months.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
7/12. 3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
8/12. Granulocytapheresis as a possible cancer treatment.We assessed the effect of granulocyte apheresis in patients exhibiting increased granulocyte-to-lymphocyte ratio in order to overcome granulocytosis occurring in the terminal stages of malignancies. 17 patients with post-operative recurrent metastatic tumors including 6 gastric, 3 colonic, 2 rectal, 1 esophageal and 5 breast cancers were selected. The granulocytapheresis was performed by extracorporeal vein-to-vein circulation equipped with an apheresis column filled with cellulose acetate beads. Each week the patients underwent one or two sessions of treatment that lasted 30 to 50 minutes per session at a flow rate of 30 to 50 ml/min. 15 sessions formed 1 therapeutic cycle. The effect of granulocytapheresis resulted in partial response (PR) in 4 cases, no change (NC) in 7 cases and partial disease (PD) in 6 cases. The performance status showed 30% remission. None of the patients exhibited significant side effects. Since the treatment demonstrated anti-tumor effects, granulocytapheresis may be applied during combined cancer treatments.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
9/12. The glutathione cycle is the creative reaction of life and cancer. Cancer causes oncogenes and not vice versa.Life is definable as a chemical reaction which obeys exponential growth and dies if reversed. Such a reaction must be the commencement of all life so that every evolved form of it inherits these characteristics. As no single reaction known has these two features, life must be a combination of two or more reactions which whilst obeying all the classical laws of physics and chemistry assume an exponential form and effectively act as being irreversible. The reactions of glutathione--oxidation and reduction--when combined in sequence as a cyclical process fulfill these criteria. The cyclic changes of glutathione from reduced to oxidised to reduced forms must therefore be the reaction which creates life and is responsible for cancer's growth. 434 mHz electromagnetic radiation stimulates cancer growth rate by forcing this cycle into activity. Proof of this hypothesis is the long-term control of cancer in 11 patients treated with oxidised glutathione and 434 mHz radiation. Genetic material does not contain any energy system with exponential form, neither is it self-replicating. Genetic material will only reproduce if placed within an immortal cell in which all controls of the glutathione system have been lost, as in a cancer cell. oncogenes must be the product of cancer and not the reverse.- - - - - - - - - - ranking = 2.5keywords = cycle (Clic here for more details about this article) |
10/12. Lhermitte's sign following chemotherapy with docetaxel.Specific causes for Lhermitte's sign (LS) in cancer patients are spinal cord compression, radiation therapy to the spinal cord, and cisplatin chemotherapy. We observed a transient LS in five of 87 patients treated with more than two cycles of 100 mg/m2 docetaxel (Taxotere). LS developed either concurrently or after the onset of docetaxel-induced sensory neuropathy, and disappeared after the discontinuation or dose reduction of chemotherapy.- - - - - - - - - - ranking = 0.5keywords = cycle (Clic here for more details about this article) |
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