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L Leong

Publications and source records attributed to L Leong.

At least 19 recordsLinked to original sources
PubMed2006

Evidence for multiple loci from a genome scan of autism kindreds.

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.

Adolescent↗
PubMed2006

Should high sensitive C-reactive protein measurement be included in health screening packages?

INTRODUCTION: The Centers for Disease Control and Prevention (CDC) and the American Heart Association (AHA) have endorsed the optional use of high sensitive C-reactive protein (hsCRP) to identify patients without known coronary heart disease but who may be at higher absolute risk than estimated by major risk factors. This study assessed the potential value of hsCRP measurement in addition to routine lipid and risk factor assessment on patient management for individuals undergoing multiphasic health screening. METHODS: hsCRP was measured on fasting lipid samples on patients attending the Health Enrichment Clinic at Tan Tock Seng Hospital between January and April 2004. These results were then compared with the outcome of individual patient risk assessment (using the 2001 Singapore Ministry of Heath Clinical Practice Guidelines on Lipids), the patient's lipid results and whether the patient was already on anti-lipid treatment. RESULTS: 212 samples were analysed for hsCRP. Seven patients were already on anti-lipid drugs. Using the AHA/CDC guidelines, hsCRP measurement would be of value in deciding management in 12.7 percent of all patients. Of this group, 11 percent had hsCRP concentrations in the high risk category. Restricting hsCRP measurement to only those patients with two or more cardiac risk factors and not on anti-lipid drugs would increase the proportion of patients where hsCRP could be useful in deciding management, to 81.8 percent. CONCLUSION: For clinicians prepared to consider treatment in patients with elevated hsCRP levels, hsCRP measurement should be included as part of health screening packages to selected patients based on individual cardiac risk assessment.

Adult↗
PubMed2005

Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14.

Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes but, given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. We report results from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program. Our definition of affection status included schizophrenia and schizoaffective disorder, depressed type and we defined families as European American (EA) and African American (AA) based on the probands' and parents' races based on data collected by interviewing the probands. We also assessed evidence for racial heterogeneity in the regions most suggestive of linkage. The maximum LOD score across the genome was 2.96 for chromosome 18, at 0.5 cM in the combined race sample. Both racial groups showed LOD scores greater than 1.0 for chromosome 18. The empirical P-value associated with that LOD score is 0.04 assuming a single genome scan for the combined sample with race narrowly defined, and 0.06 for the combined sample allowing for broad and narrow definitions of race. The empirical P-value of observing a LOD score as large as 2.96 in the combined sample, and of at least 1.0 in each racial group, allowing for narrow and broad racial definitions, is 0.04. Evidence for the second and third largest linkage signals come solely from the AA sample on chromosomes 6 (LOD = 2.11 at 33.2 cM) and 14 (LOD = 2.13 at 51.0). The linkage evidence differed between the AA and EA samples (chromosome 6 P-value = 0.007 and chromosome 14 P-value = 0.004).

Adult↗
PubMed2002

Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer.

We report on a predictive model of long-term outcome in 114 high-risk breast cancer patients treated with high-dose chemotherapy between 1989 and 1994. Paraffin-blocks from 90 of the 114 primaries were assessed for the presence of five risk factors: grade, mitotic index, protein expression of p53, HER2/neu, and oestrogen/progesterone receptor status; we could analyse the effect of risk factors in 84 of these 90 tumours. Seven-year relapse-free and overall survival was 58% (95% confidence interval 44-74%) and 82% (95% confidence interval 71-94%) vs 33% (95% confidence interval 21-52%) and 41% (95% confidence interval 28-60%) for patients whose primary tumours displayed > or =3 risk factors vs patients with < or =2 risk factors. For the entire group of 168 high-risk breast cancer patients, inflammatory stage IIIB disease and involved post-mastectomy margins were associated with decreased relapse-free survival and overall survival; patients treated with non-doxorubicin containing standard adjuvant therapy experienced worse overall survival (RR, 2.08; 95% confidence interval 1.04 to 4.16; P=0.04), while adjuvant tamoxifen improved overall survival (RR, 0.65; 95% confidence interval 0.41-1.01; P=0.054). Future trial designs and patient selection for studies specific for high-risk breast cancer patients should include appropriate prognostic models. Validation of such models could come from recently completed randomised, prospective trials.

Adult↗
PubMed2002

A deceptive cervical lymph node: a solitary spinal osteochondroma.

INTRODUCTION: Osteochondroma of the cervical spine is an uncommon bony tumour. CLINICAL PICTURE: We present a case which was misdiagnosed as a posterior cervical lymph node. The patient presented with a tender neck lump and was seen by two surgical departments. They eventually diagnosed it as an osteochondroma and referred the patient to our department. This exostosis arose from the lamina of C3 vertebra and extended posteriorly. The patient presented with persistent neck ache but had no neurological deficit. TREATMENT: It was excised uneventfully. CONCLUSION: From the literature review, this appears to be the first case where an exostosis arose from a spinal facet joint. A discussion of osteochondromas follows.

Adolescent↗
PubMed2001

Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis.

High-throughput screening for the induction of a luciferase reporter gene in a thrombopoietin (TPO)-responsive cell line resulted in the identification of 4-diazo-3-hydroxy-1-naphthalenesulfonic acids as TPO mimics. Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity. Furthermore, these compounds elicited biochemical responses in TPO-receptor-expressing cells similar to those in TPO itself, including kinase activation and protein phosphorylation. Potencies for the best compounds were high for such low molecular weight compounds (MW < 500) with EC(50) values in the region of 1-20 nM.

Animals↗
PubMed2001

Continuous infusion prochlorperazine: pharmacokinetics, antiemetic efficacy, and feasibility of high-dose therapy.

PURPOSE: The purpose of these sequential phase I studies was to evaluate the antiemetic efficacy and pharmacokinetics of high-dose continuous infusion prochlorperazine. METHODS: A total of 52 patients with advanced cancer were treated in two sequential phase I studies utilizing high-dose prochlorperazine. In study 1, designed to investigate the antiemetic effects of dose-intensive prochlorperazine, various cisplatin-based multiagent chemotherapeutic regimens were administered in combination with escalating doses of prochlorperazine. In study 2, a fixed dose of cisplatin (60 mg/m2) was administered over 24 h as a continuous intravenous infusion in combination with infusional high-dose prochlorperazine. Antiemetic efficacy in the first trial was assessed in terms of the number of episodes of nausea, retching, and/or emesis during the 24 h following cisplatin administration. The pharmacokinetics of high-dose prochlorperazine were evaluated in eight patients treated in study 2 at the two dose levels below those at which dose-limiting toxicity was noted. RESULTS: The maximally tolerated dose of prochlorperazine in combination with cisplatin (60 mg/m2 administered as a continuous infusion over 24 h) was 24 mg/h. The dose-limiting toxicity was grade 4 agitation and confusion noted in one patient treated at 26 mg/h. This patient died 3 days following cessation of chemotherapy due to the toxicity of the regimen in combination with the debilitating pulmonary effects of the disease. The mean end of infusion prochlorperazine level at the 24 mg/h dose level was 1.1 microM, a concentration previously reported to be consistent with the reversal of the multidrug resistance phenotype. Two partial responses were observed in study 2. CONCLUSIONS: We conclude that the antiemetic efficacy of high-dose infusional prochlorperazine does not appear to be improved over more convenient bolus administration. However, prochlorperazine levels consistent with those required in vitro for drug resistance reversal are attainable within the dose range having a tolerable toxicity profile.

Adult↗
PubMed2001

Phase II trial of high-dose intravenous doxorubicin, etoposide, and cyclophosphamide with autologous stem cell support in patients with residual or responding recurrent ovarian cancer.

This study was performed in order to evaluate the toxicities, progression-free and overall survival of patients with responsive residual or recurrent ovarian cancer treated with high-dose chemotherapy. Twenty-seven patients were treated. Doxorubicin, 165 mg/m(2) over 96 h (days -12 to -8), etoposide 700 mg/m(2) every day x3 (days -6 to -4), and cyclophosphamide 4.2 g/m(2) on d -3 was followed by stem cells and granulocyte colony-stimulating factor. The median days of granulocyte count <500/microl was 14 (range 10-42) and platelets <20,000/microl was 13 (range 2-80). Median numbers of red cell and platelet transfusions were 15 (5-16) and 14 (4-103). Toxicity included mucositis requiring narcotic analgesia in all patients. Asymptomatic decreases in ejection fraction to values <50% were observed in four patients. No clinical congestive heart failure was observed. One death due to sepsis was observed. Median progression-free survival is 7.5 months (1.0-56 months); five patients remain alive, two of whom remain progression-free at 19.5 and 24.5 months post transplant. Median overall survival is 14.0 months (1-68 months). We conclude that high-dose anthracyclines may be safely administered to ovarian cancer patients. The short overall and progression-free survivals observed in our population suggest that this combination is not optimal.

Adult↗
PubMed2001

Tandem-cycle high-dose melphalan and cisplatin with peripheral blood progenitor cell support in patients with breast cancer and other malignancies.

We evaluated the feasibility of tandem-cycle high-dose chemotherapy (HDCT) with cisplatin, melphalan, and peripheral blood progenitor cells (PBPCs). Fifty patients with high-risk primary (n = 17) or stage IV breast cancer (n = 29) or other malignancies (n = 4) received 2 cycles of intravenous melphalan, 20 to 151.8 mg/m2, and cisplatin, 200 mg/m2, followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF. Starting at 40 mg/m2 of melphalan, patients also received PBPCs. Delayed platelet recovery defined the maximum tolerated dose (MTD) for melphalan at 101.2 mg/m2 per cycle. There were no treatment-related deaths. Cycle 2 was delivered at a median of 1.7 months after cycle 1; 72% of patients treated at the MTD received both cycles. Cycle 2 was omitted when patients refused it or had disease progression or toxicities, primarily prolonged thrombocytopenia. Complete response rates in stage IV breast cancer patients increased from 28% pre-HDCT to 55% after cycle 2. At a median follow-up of 4.6 years (range, 1.5-8.1 years), 11 of 29 patients with stage IV breast carcinoma were alive with 5-year projected progression-free and overall survival rates of 19% (95% confidence interval [CI], 7%-41%) and 39% (95% CI, 20%-62%), respectively. Five-year projected progression-free and overall survival rates for patients with stage IV breast cancer in complete response following HDCT versus all others were 35% (95% CI, 15%-70%) versus 0% (P = .01) and 61% (95% CI, 35%-91%) versus 10% (95% CI, 2%-60%) (P = .003; log-rank test), respectively. Estrogen-receptor positivity was predictive of reduced risk of progression (relative risk [RR], 0.25; 95% CI, 0.10-0.65; P = .003) and death (RR, 0.27; 95% CI, 0.10-0.72; P = .009) after adjusting for response status. Five-year projected relapse-free and overall survival rates were 71% (95% CI, 43%-96%) and 82% (95% CI, 56%-100%), respectively, for the 17 patients with high-risk primary breast cancer. Tandem-cycle high-dose melphalan and cisplatin with PBPCs is feasible. Preliminary data suggest significant activity in selected patients with stage IV responding breast carcinoma.

Adult↗
PubMed2001

Effect of a lacto-ovo vegetarian diet on fasting small intestinal motility.

BACKGROUND: Changes in diet can alter gastric and small intestinal (SI) motility. The effects of a vegetarian diet on fasting SI motility are unknown. METHODS: Manometric studies were performed in 9 lacto-ovo vegetarians (7 women) and 9 omnivores (7 women) of similar age and body mass index. On each study day, manometry was used to assess SI motility for 5 h, or 3 complete cycles of the interdigestive motor complex (IDMC). Lacto-ovo vegetarians were studied once: omnivores were studied twice, on their usual diet, and after consuming a 14-day lacto-ovo vegetarian diet. Diet diaries were kept for 5 days prior to each manometric study. Data were analysed for dietary composition and for cycle length and duration of each phase (I, II and III) of the IDMC. RESULTS: Dietary intake did not differ between chronic vegetarians and chronic omnivores apart from a trend to higher fibre intake (29 +/- 3 versus 20 +/- 3 g/day; P = 0.058). Omnivores eating a vegetarian diet showed a trend to decreased alcohol consumption (P = 0.068), but did not increase their fibre intake (20 +/- 3 versus 21 +/- 3 g/day). Neither cycle length nor duration of each IDMC phase differed between chronic vegetarians and chronic omnivores. After 14 days of a vegetarian diet, omnivores had a reduction in cycle length (128 +/- 19 versus 86 +/- 12 min; P = 0.02), with a non-significant reduction of Phase II (99 +/- 20 versus 50 +/- 8 min: P = 0.066). CONCLUSIONS: A chronic vegetarian diet has no major effect on fasting SI motility; but acute dietary change may alter the cycle length and component phases of the IDMC.

Adolescent↗
PubMed2001

Using gadolinium-infusion MR venography to show the impalpable testis in pediatric patients.

UNLABELLED: OBJECTIVE; This study evaluated the adjunctive value of gadolinium-infusion MR venography to locate the impalpable testis. SUBJECTS AND METHODS: Routine MR imaging and MR venography were performed in 34 patients presenting with impalpable testis. MR venography was performed by dynamic injection of gadopentetate dimeglumine bismethylamide with images taken at delayed venous phases. The site of the testis was determined by detection of the contrast-enhanced pampiniform venous plexus. RESULTS: A total of 44 impalpable testes were examined. Twenty-six hypoplastic canalicular testes, two testes at pelvic skinfold, four atrophic testes in the scrotum, and five intraabdominal testes were detected on both routine MR imaging and MR venography. Five "vanishing" testes in the scrotum and two at the groin region were detected by MR venography but not on MR imaging. CONCLUSION: Gadolinium-infusion MR venography is superior to MR imaging in the detection of atrophic testes. The method is a useful adjunct in patients with negative MR imaging findings.

Adolescent↗
PubMed2001

Phase I trial of 96-hour continuous infusion of dexrazoxane in patients with advanced malignancies.

Dexrazoxane is a bidentate chelator of divalent cations. Pretreatment with short infusions of dexrazoxane prior to bolus doxorubicin has been shown to lessen the incidence and severity of anthracycline-associated cardiac toxicity. However, because of rapid, diffusion-mediated cellular uptake and the short plasma half-life of dexrazoxane, combined with prolonged cellular retention of doxorubicin, dexrazoxane may be more effective when administered as a continuous infusion. Thus, a Phase I pharmacokinetic trial of a 96-h infusion of dexrazoxane was performed. Dexrazoxane doses were escalated in cohorts of 3 to 6 patients per dose level. All patients received granulocyte-colony stimulating factor at a dose of 5 microg/kg/day starting 24 h after completion of the dexrazoxane infusion. Plasma samples were collected and analyzed for dexrazoxane by high-performance liquid chromatography. Urine collections were performed at baseline and during the infusion to determine the renal clearance of dexrazoxane and the excretion rate of divalent cations. Twenty-two patients were enrolled at doses ranging from 125 to 250 mg/m(2)/day. Grade 3 and 4 toxicities included grade 4 thrombocytopenia in 2 patients treated at 250 mg/m(2)/day, grade 3 thrombocytopenia and grade 4 nausea and vomiting in 1 patient treated at 221 mg/m(2)/day, grade 4 diarrhea and grade 3 nausea and vomiting in 1 patient treated at 221 mg/m(2)/day, and grade 3 hypertension in 1 patient treated at 166.25 mg/m(2)/day. Steady-state dexrazoxane levels ranged from 496 microg/l (2.2 microM) to 1639 microg/l (7.4 microM). Dexrazoxane plasma CL(ss) and elimination t(1/2) were 7.2 +/- 1.6 l/h/m(2) and 2.0 +/- 0.8 h, respectively. The mean percentage of administered dexrazoxane recovered in the urine at steady state was 30% (range, 10-66%). Urinary iron and zinc excretion during the dexrazoxane infusion increased in 12 of 18 and 19 of 19 patients by a median of 3.7- and 2.4-fold, respectively. These results suggest that dexrazoxane as a 96-h infusion can be safely administered with granulocyte-colony stimulating factor at doses that achieve plasma levels that have been demonstrated previously to inhibit topoisomerase II activity and to induce apoptosis in vitro. Additional studies will be required to determine whether the combination of continuous infusions of dexrazoxane and doxorubicin would provide enhanced cardioprotection compared with the currently recommended bolus or short infusion schedules.

Aged↗
PubMed2000

Phase II trial of combination intraperitoneal cisplatin and 5-fluorouracil in previously treated patients with advanced ovarian cancer: long-term follow-up.

OBJECTIVES: This trial was performed to determine the response rate and progression-free and overall survivals of patients with advanced recurrent ovarian cancer who were treated with intraperitoneal cisplatin and 5-fluorouracil. METHODS: Twenty-four patients with ovarian cancer were entered on this trial and treated with intraperitoneal (ip) cisplatin (DDP) and ip 5-fluorouracil, every 3 weeks for eight cycles. Following iv hydration, the cisplatin and 5-fluorouracil were administered through an ip catheter in 2 liters of 0.9% normal saline with a 4-h dwell. RESULTS: All patients were evaluable for progression-free and overall survival and toxicity analysis, and 22 patients for response. The median age was 59 (range, 35-71); initial disease status included 9 patients with residual disease following chemotherapy prior to entry on this study; 5 patients had progressed, and 10 patients had recurrent disease more than 6 months following initial chemotherapy. Of the 9 patients with residual disease, 1 complete response and 3 partial responses were observed; of 10 patients with recurrent disease, 1 complete and 1 partial response were observed for an overall response rate of 27%. No objective responses were seen in the 7 patients who were platinum-refractory on protocol entry. The median progression-free and overall survivals are 7.0 (range, 0.5-137) and 15.5 (range, 3-147) months, respectively. Toxicity included hypomagnesemia, vomiting, abdominal pain, and mild anemia. Only one patient required a dosage adjustment of cisplatin for a serum creatinine elevation >2.0 mg/dl. CONCLUSIONS: We conclude that the combination of ip cisplatin and 5-FU is an effective regimen for patients with residual or relapsed epithelial ovarian cancer with survival durations, response rates, and toxicity profiles that compare favorably with those of other second-line ovarian cancer regimens. Patients who are primarily platinum-refractory are unlikely to benefit from these agents administered into the peritoneal cavity.

Adult↗
PubMed2000

Differential expression of N- and B-cadherin during lens development.

PURPOSE: To analyze the dynamics of N- and B-cadherin cell adhesion molecule expression and cytoskeletal interaction during embryonic chick lens development. METHODS: Localization of N- and B-cadherin, F-actin, and connexin 56 were determined by immunohistochemistry of developing lenses or immunocytochemistry of differentiating primary lens cultures. Biochemical analysis of cytoskeletal linkage of N- or B-cadherin was assessed by differential detergent extraction, electrophoresis, and immunoblotting. RESULTS: The results indicate that although both cadherins are expressed throughout lens development, N-cadherin expression detected was similar in both lens epithelial and fiber cells, whereas B-cadherin was preferentially localized to the lens fiber cells. During differentiation, both cadherins become increasingly associated with the lens cytoskeleton, as indicated biochemically by a transition from largely Triton X-100-soluble to Triton X-100-insoluble pools and immunocytologically by cadherin localization to cell-cell borders and colocalization with the actin cytoskeleton. Although a significant fraction of N-cadherin remains Triton X-100-soluble as the lens cells differentiate, B-cadherin becomes resistant to extraction by both Triton X-100 as well as RIPA buffers. As detected immunocytochemically in lens cell cultures, the temporal localization of N-cadherin to cell-cell interfaces precedes that of B-cadherin. Furthermore, temporal localization of B-cadherin, as opposed to N-cadherin, to cell-cell borders more closely parallels that of connexin 56 in vitro as well as in vivo. CONCLUSIONS; These results suggest that while both N- and B-cadherin are expressed during lens cell differentiation, both their patterns of expression as well as their cytoskeletal association differ between epithelial and fiber cells.

Actins↗
PubMed1999

Recombinant human thrombopoietin in combination with granulocyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy.

Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 micrograms/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 micrograms/kg on days -3, -1, and 1, or 0.6 micrograms/kg on days -1 and 1. G-CSF, 5 micrograms/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34(+) cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 10(6)/kg (range, 1.3 to 17.6) versus 0.8 x 10(6)/ kg (range, 0.3 to 4.2), P =.0003. The targeted minimum yield of 3 x 10(6) CD34(+) cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P =.001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P =.0001) and platelet recovery (day 9 v 10, P =.07) were accelerated, and fewer erythrocyte (3 v 4, P =.02) and platelet (4 v 5, P =.02) transfusions were needed compared with G-CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P <.0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 microgram/kg. rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.

Adult↗
PubMed1999

Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up.

Forty-three patients with ovarian cancer were entered on this trial and treated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and intraperitoneal (ip) cisplatin (DDP), every 21 days for eight cycles. Following iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are evaluable for overall and progression-free survival with a median follow-up of 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (range 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were stage III (optimally debulked), 14 patients were stage III (suboptimally debulked), and 7 patients were stage IV. Two patients had received prior alkylator therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally debulked stage III patients, there were 7 complete responses, 3 partial responses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 suboptimally debulked stage III patients there were 4 complete responses, 4 partial responses, 3 with stable disease, 2 progressions on treatment, and 1 inevaluable patient. Five-year progression-free and overall survivals for stage III optimally debulked patients are 21 and 64%, respectively. At 10 years, progression-free and overall survivals for this group are 21 and 29%, respectively. Toxicity included neutropenia (complicated by sepsis in 2 patients), infrequent thrombocytopenia, and mild anemia. Three patients developed transient serum creatinine elevations >2.0 mg/dl; however, decreased creatinine clearance was noted in 93/258 (36%) of evaluable courses which required a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free and overall survivals that compare favorably with those of other published studies of intravenous or intraperitoneal chemotherapy. This report is unusual in terms of the prolonged follow-up for all patients enrolled. These long-term results lend further support to recently published trials documenting the efficacy of intraperitoneal chemotherapy for patients with this disease.

Adult↗