A rapidly developing violaceous plaque.
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Aged↗
Biomedical subjects
M Christian
Publications and source records attributed to M Christian.
Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers.
Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
Administration, Oral↗
A phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary.
We have conducted a disease specific phase I study of paclitaxel and cyclophosphamide in recurrent adenocarcinoma of the ovary. This was done to take advantage of the cellular and molecular synergism between paclitaxel and DNA-damaging agents, with the hope of avoiding paclitaxel-cisplatin toxicities. Paclitaxel was given as a 24-hr CIVI, after which cyclophosphamide was given as a 60-min infusion. Cycles of therapy were repeated every 3 weeks; and granulocyte colony-simulating factor (G-CSF) was given in a "flexible" dosing fashion. Starting doses were 170 mg/m2 paclitaxel and 750 mg/m2 cyclophosphamide. Dose-limiting toxicity (DLT) was seen at the doses of 250 mg/m2 paclitaxel and 1250 mg/m2 cyclophosphamide. DLT was cumulative thrombocytopenia. There were six nonhematologic grade 3 or 4 toxicities experienced in the study. Eleven of 20 evaluable patients (55%) have achieved an objective response (4 CCR;7 PR). Three of four CCRs were confirmed by negative findings at peritoneoscopy. The median number of prior therapies was 2 (range 1-4) and 17 individuals had platinum-refractory disease. We conclude that paclitaxel followed by cyclophosphamide is an active combination in recurrent ovarian cancer and that further study is needed to determine if this combination is truly better than paclitaxel alone.
Adenocarcinoma↗
A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer.
Epithelial ovarian cancer patients with bulky residual tumor have a poor response to therapy and limited survival. We investigated the addition of dose-intense paclitaxel to cisplatin and cyclophosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m2 and administered in combination with cisplatin at > or = 75 mg/m2 and cyclophosphamide at 750 mg/m2. Thirty-one of 36 patients (86%) and 25 (70%) had > or = 2 and > or = 3 cm residual disease after surgery, respectively. One-third had stage IV disease, and 80% had grade 3 tumors. The maximally tolerated doses (MTD) were paclitaxel at 250 mg/m2, cisplatin at 75 mg/m2, and cyclophosphamide at 750 mg/m2 on a 21-day cycle with G-CSF, 10 micrograms/kg/day. Administered dose intensity at the MTD was > or = 86%. Reversible grade 3 peripheral neuropathy occurred in 28% of patients and fever during neutropenia in 2/352 cycles (0.5%). The pathologic response rate is 36% with an additional 25% having minimal microscopic disease. Median progression-free and overall survivals for patients receiving paclitaxel at 250 mg/m2 at a median potential follow-up of 22 months have not been reached for the cohort nor for the > or = 3-cm subgroup. This regimen should be evaluated in a prospective, randomized clinical trial.
Adult↗
Paclitaxel activity in heavily pretreated breast cancer: a National Cancer Institute Treatment Referral Center trial.
PURPOSE: To provide paclitaxel, an investigational drug at the inception of this study, to women with chemotherapy-refractory metastatic breast cancer and to evaluate response and toxicity in these patients. PATIENTS AND METHODS: Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastatic breast cancer and a contraindication to further doxorubicin treatment received paclitaxel either at 175 mg/m2 intravenously (IV) over 24 hours or at 135 mg/m2 if they had prior irradiation to 30% of marrow-bearing bone or a cumulative dose of mitomycin > or = 20 mg/m2. RESULTS: In a subgroup of patients (n = 172) with measurable disease, four complete responses (CRs) and 36 partial responses (PRs) occurred, for an overall response rate of 23% (95% confidence interval [CI], 17% to 30%). No differences in response rates were noted according either to the number of prior chemotherapy regimens received or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutropenia in 45% of patients and a hospitalization rate of 49%. CONCLUSION: Paclitaxel's activity in this multiinstitutional trial in heavily pretreated patients confirms the encouraging results attained in single-institution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative care, supportive measures such as colony-stimulating factors and antibiotics were not used prophylactically. Current research efforts are focusing on whether paclitaxel's activity against breast cancer is dose- and/or schedule-dependent, and on what role it has in patients with less advanced disease.
Adult↗
Familial occurrence of cutaneous T cell lymphoma: a case report of monozygotic twin sisters.
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Female↗
Clinical trials referral resource. Clinical trials of suramin.
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Antineoplastic Agents↗
Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer.
BACKGROUND: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer. PURPOSE: Our purpose was to conduct a phase II clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). METHODS: A prospective phase II clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 micrograms/kg per day was given to ameliorate myelo-suppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 micrograms/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. RESULTS: Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. CONCLUSIONS: We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer.
Adult↗
Validity and reliability testing of the Prenatal Psychosocial Profile.
Two studies of low-income pregnant women (N = 179) were done to examine the validity and reliability of the Prenatal Psychosocial Profile (PPP). The PPP, a composite of the Rosenberg Self-Esteem Scale, the Support Behaviors Inventory, and a newly developed measure of stress, is a brief, comprehensive clinical assessment of psychosocial risk during pregnancy. Construct validity of the stress scale was supported by theoretically predicted negative correlations with self-esteem, partner support, and support from others (N = 91). Convergent validity of the stress scale was demonstrated by a correlation of .71 with the Difficult Life Circumstances Scale. Adequate levels of internal consistency were found. Interrelationships between the four subscales were consistent with the underlying conceptualization, and there was beginning evidence of the factorial independence of the subscales.
Adolescent↗
Evidence of an absorption phase after short intravenous suramin infusions.
Suramin was given as an intravenous infusion to 16 cancer patients in a phase I trial. Individual pharmacokinetic parameters were calculated from a test dose given 1 week prior to the administration of a full-dose (350-700 mg/m2) regimen of 1-h loading and maintenance infusions. A distribution phase of 3.8 h was found. Plasma suramin concentrations were noted to increase following cessation of the intravenous test infusion in eight subjects. A model is proposed in which high-capacity, low-affinity binding of suramin to a shallow compartment adjacent to the intravascular space occurs rapidly during infusion, followed by absorption back into the measured blood pool with binding to plasma albumin. Despite the observable presence of this postinfusion peak shortly after the cessation of the brief suramin infusion, the pharmacokinetics of suramin were best characterized by a traditional two-compartment model. The dose-adjusted area under the concentration-time curve (AUC) increased with dose, supporting a hypothesis of sustained absorption of suramin to vascular endothelium but also raising the possibility of dose-dependent clearance.
Absorption↗
The absence of cumulative bone marrow toxicity in patients with recurrent adenocarcinoma of the ovary receiving dose-intense taxol and granulocyte colony stimulating factor.
Forty-eight patients with recurrent adenocarcinoma of the ovary were treated with taxol and granulocyte colony stimulating factor (G-CSF), with a target taxol dose intensity of 250 mg/m2 every 3 weeks (83.3 mg/m2/week). We have assessed the patterns of granulocyte and platelet toxicity seen in this cohort. Individual patients received up to nine cycles of therapy. Criteria for entry onto protocol included good end organ function, good performance status and the absence of substantial co-morbid disease. Mean taxol dose intensity was 79.0 mg/m2/week for the whole cohort and did not diminish with increased duration of therapy. Granulocytopenia and thrombocytopenia were well controlled, with the average duration of platelet and neutropenic nadirs being less than 1 day for all cycles. There was no evidence of cumulative toxicity for granulocytes nor platelets, for up to eight cycles of therapy. We conclude that taxol, when given with G-CSF support, can be safely administered in a dose-intense fashion for multiple cycles of therapy, without cumulative bone marrow toxicity.
Adenocarcinoma↗
New chemotherapeutic agents in non-small-cell lung cancer.
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Aminopterin↗
A reassessment of cardiac toxicity associated with Taxol.
Cardiac toxicity was first noted in patients receiving Taxol during continuous cardiac monitoring, which was performed because of the high incidence of serious hypersensitivity reactions noted early in phase I trials. After cardiac events were documented, patients with cardiac disease and those on medications known to alter cardiac conduction were excluded from most trials. The cardiac events reported with Taxol from the initiation of NCI-sponsored clinical trials through August 1992 are summarized. Adverse cardiac events were reviewed in four clinical databases: 1) the Cancer Therapy Evaluation Program's Adverse Drug Reaction database following treatment of more than 3400 patients; 2) all cardiac toxicities in patients on GOG-111 who were randomized to cisplatin plus either Taxol or cyclophosphamide; 3) cardiac toxicity in 198 patients who received 618 courses of Taxol with or without cisplatin during continuous cardiac monitoring; and 4) cardiac toxicities reported for the first 696 patients on NCI TRC-9103 for ovarian cancer. Published reports of studies of taxine's cardiac effects, and of cardiac toxicity associated with yew poisoning, Cremophor EL, and H1 and H2 antagonists, are also reviewed. In patients without significant cardiac risk factors, asymptomatic sinus bradycardia is frequent (approximately 30%). Heart block and conduction abnormalities occur infrequently and are often asymptomatic. The casual relationship of Taxol to atrial and ventricular arrhythmias and cardiac ischemia is less clear because many patients had other conditions known to be associated with cardiac events. Nevertheless, the incidence of serious cardiac events was low. Routine cardiac monitoring is not required for patients without risk factors. There are, however, insufficient data to make treatment recommendations for patients with cardiac disease and those taking medications that alter cardiac conduction. To maximize patient safety and the clinical database, physicians who administer Taxol should continue to be alert to potential cardiac toxicities associated with Taxol.
Animals↗
Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy.
PURPOSE: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. PATIENTS AND METHODS: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). RESULTS: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. CONCLUSION: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.
Adult↗
Transmission of health information on leprosy from children to their families: another approach to health education.
A controlled study was carried out in the North Arcot District of Tamil Nadu, South India to determine whether health information given to schoolchildren would influence the knowledge and attitudes of their families concerning leprosy. A total of 41 children and almost all of their household members participated in the study. The study, conducted by questionnaire, involved a pre-test of knowledge and attitude about leprosy of seventh standard students and their families. After one group of children received health education about leprosy and the other received information about tuberculosis, an identical post-test questionnaire was administered to all participants. Although significant improvement in knowledge about leprosy was detected in the leprosy educated group of children compared with controls, no transmission of information on leprosy was detected in the family members of either group. The attitudes of the children who had been educated about leprosy may have been adversely affected by the health education session. The reasons for our failure to detect significant transfer of information about leprosy in this setting are discussed, as well as the need for additional research in this area.
Adolescent↗
Controlled clinical trial of two multidrug regimens with and without rifampin in highly bacilliferous BL/LL south Indian patients: a five-year report.
A controlled clinical trial of two multidrug regimens in multibacillary lepromatous and near-lepromatous patients with a bacterial index (BI) of 2.5 or more was conducted. Patients were randomly allocated to either a two-drug regimen of dapsone plus clofazimine for 60 months or a four-drug regimen of rifampin, isoniazid, dapsone, and clofazimine for the first 3 months and clofazimine plus dapsone for the next 57 months. There was no difference between the rifampin and nonrifampin regimens with respect to the clinical improvement or bacteriological status of the patients at 60 months. Reactive states and neuritis were observed to be equal in the two patient groups.
Adolescent↗
Relapse or late reversal reaction?
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Antibodies, Monoclonal↗