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Biomedical subjects

C Tan

Publications and source records attributed to C Tan.

At least 91 records · Page 5Linked to original sources
PubMed1991

A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors.

A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72-hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high-grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P less than 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study.

Adult↗
PubMed1991

Basis for natural resistance to methotrexate in human acute non-lymphocytic leukemia.

The basis of intrinsic resistance of blasts from patients with acute non-lymphocytic leukemia (ANLL) to methotrexate was studied. MTX polyglutamate formation was measured in blast cells from 19 patients with ANLL and in 7 pediatric patients with acute lymphocytic leukemia (ALL), after in vitro incubation for 24 h with 3H-methotrexate. There was no significant differences seen in the total amount of MTX plus polyglutamates measured between ANLL and ALL blasts, indicating that transport defects do not account for intrinsic MTX resistance in ANLL. However, there were significant differences between the amounts of long chain MTX polyglutamates found in ANLL cells as compared to ALL cells. Most, but not all, ANLL blasts were unable to form long chain polyglutamates. In as much as the level of MTX polyglutamates found in blast cells after MTX administration allows for retention of this drug, this property may explain, at least in part, the refractoriness of most patients with ANLL to methotrexate.

Adolescent↗
PubMed1991

Correction of constriction rings.

A refinement in the correction of deep and shallow constriction rings, in which subcutaneous fat and fascial flaps are advanced into the defect to prevent recurrent contour deformities, is presented. A straight-line dorsal closure is preferred, with Z-plasties placed along the side of the digits, forearm, or arm. Long-term follow-up is presented in 58 patients with 116 constriction rings corrected by either traditional serial Z-plasties of skin (n = 61 rings) or this new method of contour correction (n = 55 rings). Specific correction of soft tissue is recommended when tissue is available.

Adipose Tissue↗
PubMed1991

Alterations in self-perceptions among adolescent cancer survivors.

Psychosocial adjustment in adolescent cancer survivors has been documented to be quite variable. Factors mediating adjustment need to be identified. The current study is an exploration of the impact that cancer diagnosis and treatment has on adolescent's self-perceptions and the role this has in mediating adjustment in this group. Fifty-eight adolescent survivors of hematologic malignancies were interviewed about alterations in self-perceptions related to their cancer experience and completed a cancer-specific social problem-solving task. Initial findings suggest that cancer universally alters the way adolescent survivors view themselves, but that the alteration can be both positive or negative depending on the meaning ascribed to it.

Adaptation, Psychological↗
PubMed1990

Serum tumor marker half-life during chemotherapy allows early prediction of complete response and survival in nonseminomatous germ cell tumors.

The prognostic value and therapeutic utility of monitoring the decay of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) after chemotherapy for nonseminomatous germ cell tumors was assessed. Patients treated on successive front line chemotherapy protocols at Memorial Hospital between 1979 and 1988 were studied. Marker values taken within the first 90 days of treatment were reviewed for the 198 patients who had initially abnormal values and serial measurements at Memorial Hospital. Since markers frequently increased in an unpredictable fashion in the first week after chemotherapy, prechemotherapy values would be inaccurate for assessment of subsequent half-life. Therefore, the first two values measured greater than 7 days after the start of treatment were used for all calculations of half-life. Among 38 patients who had the two successive AFP measurements elevated, those who later achieved a complete response (CR) had a median AFP half-life of 6.1 days (n = 20), whereas those not achieving CR had a median AFP half-life of 13.3 days (P = 0.02). Among 37 patients with the two successive HCG values elevated, those who later achieved CR had a median HCG half-life of 4.2 days (n = 10), whereas those not achieving CR had a median HCG half-life of 18.4 days (P = 0.04). Forty-two patients who had an AFP half-life greater than 7 days or an HCG half-life greater than 3 days had significantly shorter overall survival (median, 8 months) than the other 156 patients (median not reached) (P less than 0.0001). These 42 patients also achieved CR in lower proportion (29%) than the other 156 patients (89%) (P less than 0.0001). Cox regression identified prolonged marker half-life as the most significant independent predictor of survival. Lack of appropriate decay of serum tumor markers can identify patients unlikely to achieve CR or prolonged survival and thus can be used to select patients during treatment who may benefit from an early change to more aggressive therapy.

Adolescent↗
PubMed1990

Primary colorectal sarcoma. A retrospective review and prognostic factor study of 50 consecutive patients.

Fifty patients were admitted to Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, NY, with primary colorectal sarcoma between 1948 and 1987. Thirty-one patients (62%) presented with a high-grade tumor, 37 patients (74%) with a tumor larger than 5 cm, and 12 patients (24%) with metastasis. The median survival of the whole group was 33 months, and the median survival of patients who underwent curative operation was 174 months. Nineteen of 32 patients who underwent curative operation were observed to develop distant metastasis after 3 to 209 months. The dominant sites of metastatic disease were the liver and peritoneal cavity. In a multivariable analysis, noncurative treatment and high-grade tumor were the only prognostic factors unfavorably affecting tumor-related mortality. If the type of treatment received was not considered, presentation with metastatic disease and a high-grade tumor were the two unfavorable characteristics that had independent prognostic value. Patients with a tumor that was larger than 5 cm or that was located in the colon had a greater likelihood of having a palliative procedure or high-grade tumor.

Adolescent↗
PubMed1990

The role of protamine dose assay in reversal of heparin following extracorporeal circulation for open heart surgery.

The amount of protamine required for the neutralisation of heparin following cardiopulmonary bypass was determined by a Protamine Titration Assay using the principle of the dose--response curve and the patient's estimated blood volume. In 300 open heart surgery patients, infusion of the determined dose of protamine normalised the Activated Clotting Time (ACT) to baseline levels in 97% of these patients and produced adequate hemostasis. Our present study showed that the dose of protamine dropped to 75% of the dose calculated by conventional method of heparin to protamine ratio of 1:1. This had minimised the adverse effects of excessive protamine administration and optimised coagulation control after extracorporeal circulation.

Adolescent↗
PubMed1989

Phase I trial and pharmacokinetic evaluation of fazarabine in children.

A phase I trial of fazarabine (1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 16 children with refractory malignancies. Dose-limiting toxicity consisting of reversible granulocytopenia and thrombocytopenia was observed in 4 of 4 solid tumor patients treated at the starting dose of 20 mg/m2/h. Subsequent patients were treated at a dose of 15 mg/m2/h which was determined to be the maximum tolerated dose. Moderate nausea and vomiting were the only other toxicities observed. Plasma steady-state concentrations of fazarabine were attained by 2-4 h in all patients and were 1.8 and 2.5 microM at the 15- and 20-mg/m2/h doses, respectively. The total body clearance of fazarabine was 571 and 550 ml/min/m2 at the 15- and 20-mg/m2/h doses, respectively. In three of four patients evaluated, fazarabine was detectable in the cerebrospinal fluid (CSF). Steady-state CSF concentrations ranged from 0.29 to 0.74 microM in these three individuals and the steady-state CSF:plasma ratios ranged from 0.22-0.25. Both the plasma and CSF steady-state concentrations were within the 0.1 to 1 microM range reported to be cytotoxic in vitro against the Molt-4 human T-lymphoblastic leukemia cell line. Based on the above, the optimal dose for phase II trials of fazarabine administered as a 24-h infusion is 15 mg/m2/h (360 mg/m2/day).

Antimetabolites, Antineoplastic↗
PubMed1989

Reinduction therapy for advanced or refractory acute lymphoblastic leukemia of childhood.

Thirty-four children after multiple relapse or with refractory acute lymphoblastic leukemia were treated with two novel combinations of high-dose cytosine arabinoside, methotrexate, asparaginase, vincristine, and prednisone. The first combination was given to 19 patients. Oncolytic response and marrow hypoplasia was achieved in all. There were four early infectious deaths. Thirteen of the remaining 15 (87%) in whom the response to therapy could be evaluated achieved complete remission. Two achieved good partial remissions. The median duration of complete remission and survival on study was 8 and 10 months, respectively. The four proven and three suspected fungal infections seen in the initial 19 patients was the major toxicity observed. The therapy was modified in the last 15 patients to retain efficacy while reducing the period of neutropenia from a median of 28 to 22 days. No deep-seated fungal infections were seen in these patients. Twelve (80%) achieved a complete remission. Three had an oncolytic response without achieving remission. Eighty-three percent of the 30 evaluable patients, or 74% of all patients entered on study, achieved remission. It is anticipated that the therapy described here will not only achieve another remission in the majority of patients with advanced ALL but that the patients will be able to proceed to alternate therapies with potentially more durable benefit.

Adolescent↗
PubMed1989

[Investigation into the effect of citric and phosphoric acids on planed root surfaces using S.E.M].

The aim of the present study was to evaluate the effect of citric and phosphoric acid conditioning the diseased root surface on periodontally extracted teeth. Citric acid pH1 and 50 per cent phosphoric acid were topically applied to thoroughly scaled and planed root surfaces for one to three minutes. The specimens were then processed for scanning electron microscopy (S.E.M.) Root surfaces that had received acid treatment after root planing exhibited no smear layer and the overall surface appeared to have an undulating morphology. Whereas, examination of nonacid-treated specimens showed the presence of a smear layer. Furthermore, phosphoric acid treated surfaces demonstrated more irregularity with increasing application time.

Acid Etching, Dental↗
PubMed1987

Primary cutaneous aspergillosis associated with Hickman intravenous catheters.

We describe nine patients with underlying hematologic cancer in whom primary cutaneous aspergillosis developed at the sites of Hickman intravenous catheters. Our patients, 17 to 74 years of age, were all immunocompromised either from their primary disease or from chemotherapy, and the Hickman catheters had been placed to provide venous access for chemotherapy or hyperalimentation or both. Clinical signs of infection included erythema, induration, and cutaneous or subcutaneous necrosis at the point of entry into the subclavian vein, in the subcutaneous tunnel, or at the exit site from the skin. Diagnosis was confirmed by positive wound culture for Aspergillus flavus in all but one patient. Treatment consisted of intravenous amphotericin B, oral flucytosine, and local wound care. Three patients recovered completely without operative débridement; three others recovered after operative débridement and delayed grafting. Two patients died of disseminated aspergillosis, and one died of unrelated causes while recovering from primary cutaneous aspergillosis. Successful treatment required resolution of aplasia or leukopenia, catheter removal, systemic treatment with amphotericin B, and local wound care. We conclude that primary cutaneous aspergillosis, a rare infection, may occur at the sites of Hickman catheters in immunocompromised patients, and that it is a serious complication requiring prompt diagnosis and treatment.

Adolescent↗
PubMed1987

Pediatric phase I trial and pharmacokinetic study of trimetrexate.

Trimetrexate, a new nonclassical antifolate, was evaluated in a phase I trial in children with refractory cancer including nine with acute leukemia and 21 with solid tumors. The drug was administered as an i.v. bolus injection weekly for three doses, and courses were repeated every 28 days. The dose ranged from 35 to 145 mg/m2. Thirty patients who received a total of 33 courses were evaluable for toxicity, including 19 who were evaluable for hematological toxicity. The maximally tolerated dose for patients with a solid tumor and leukemia was 110 mg/m2. The dose-limiting toxicities were myelosuppression, mucositis and a pruritic, diffuse maculopapular rash. Other side effects observed included transient, mild elevations of serum transaminases, mild nausea and vomiting, and a local phlebitis at the site of injection at higher dose levels. A single patient with delayed drug clearance had evidence of renal toxicity with a transient increase in serum creatinine. The pharmacokinetics of trimetrexate were studied in 25 patients over the entire dose range. There was considerable interpatient variability in total drug clearance (range 9.2 to 215 ml/min/m2) and half-life (2.1 to 20 h). There was a suggestion of a correlation between plasma concentration at 24 h and the development of hematological toxicity at the highest dose level. Trimetrexate was cleared primarily by biotransformation with renal clearance accounting for only 10% of total clearance. Two metabolites of trimetrexate which inhibit the enzyme dihydrofolate reductase were identified in the urine. One of these appears to be a glucuronide conjugate.

Adolescent↗
PubMed1987

PCNU and recurrent childhood brain tumors.

PCNU, the latest nitrosourea analogue to be subjected to clinical trials, held promise as a superior chemotherapy agent for brain tumors because of more favorable biochemical and cytotoxic characteristics in laboratory studies. Thirty-nine children with a variety of recurrent primary CNS tumors, all of whom had evaluable disease, participated in a phase II PCNU trial. Their mean age was 9.7 (3-20) years. PCNU was administered as a 2 hour intravenous infusion in one of 2 dose schedules at 6-7 week intervals; 100-125 mg/m2 for minimally treated patients and 70-90 mg/m2 for heavily treated patients. Response was assessed after 2 courses of chemotherapy after attempting to taper the steroid dose. The overall objective response rate was 18% (7/39) for a mean of 5.9 months (2+ -12). Only partial responses were observed. Disease-specific responses rates were: brainstem glioma--18% (3/17); cerebral glioma--27% (3/12); ependymoma--1/1; and primitive neuroectodermal tumors--(0/9) including 5 medulloblastomas, 2 pineoblastomas and 3 cerebral primitive neuroectodermal tumors. Toxicity was primarily hematologic and clinically significant thrombocytopenia (less than 50,000 mm3) was encountered in 30/38 (79%) patient trials. Modest activity of PCNU in recurrent childhood gliomas is confirmed. Our response rates, using objective CT criteria, are somewhat lower than those reported for BCNU and CCNU. Because of comparable hematologic toxicity and efficacy, intravenous PCNU does not appear to offer a clinical advantage to existing nitrosoureas for children with recurrent brain tumors using a 2 hour intravenous infusion schedule.

Adolescent↗
PubMed1987

Carboplatin and recurrent childhood brain tumors.

Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.

Adolescent↗
PubMed1984

Involved field (IF) irradiation with or without chemotherapy in the management of children with Hodgkin's disease.

The present policy at Memorial Sloan Kettering Cancer Center (MSKCC) of treating children with Hodgkin's disease [HD] is as follows: involved field (IF) irradiation only (3,600 rad) for Stages IA and IIA; IF irradiation (2,400 or 2,000 rad) combined with multidrug chemotherapy (MDP) protocol for all other stages. A somewhat higher recurrence rate is accepted for Stages IA and IIA in view of the good salvage rate for these recurrences and in view of side effects of more aggressive types of radiation treatment. One hundred forty-two patients with HD, 2-19 years of age, were treated at MSKCC between 1970 and 1981; 98 of these were treated according to the present policy (SP group), and 44 (NP group) were treated differently. All SP patients underwent staging laparotomy. The follow-up time was 12 to 146 months with a median of 65 months; two patients were lost to follow-up. For the SP group, all stages, 10-year disease-free survival is 77%, and 10-year survival is 93%. By comparison, in the NP group 10-year disease-free survival is 64%, and 10-year survival is 80%. The disease-free survival of SP patients in Stages IA and IIA treated with IF radiation alone is 72%, and survival is 95%. The disease-free survival of SP patients in advanced stages treated with combined radiation and chemotherapy is 87%; the salvage rate of recurrent disease in these stages is poor. The survival was apparently better (P = 0.07) in the SP group as compared to the NP group. All 6 patients of the SP group who died had a nodular sclerosing type of HD. None of the patients in the SP group have developed secondary malignancies, and no severe bone growth retardations or late effects to other organs were observed. In our opinion, IF irradiation alone might at present be suitable treatment for children in Stages IA and IIA of Hodgkin's disease, and addition of IF radiation with low doses of MPD improves the survival of patients in advanced stages.

Adolescent↗