Expert clinical consulting for early drug development programs in Korea

No abstract available.

Spinal Tuberculosis in Children: Predictable Kyphotic Deformity after Cure of the Tuberculosis / 대한정형외과학회잡지

PURPOSE: To assess the chronological changes of disease-related kyphosis after chemotherapy alone. MATERIALS AND METHODS: A total of 101 children aged 2 to 15 years with spinal tuberculosis, accompanied by various stages of disease processes were enrolled for analysis. By utilizing the images in them, the growth plate condition and chronological changes of kyphosis after chemotherapy were analyzed at two points in time; the first assessment was at post-chemotherapy one-year and second at the final discharge. RESULTS: Complete disc destruction in the cervical, dorsal and lumbosacral spines was observed in 2 out of 40 children (5.0%), 8 out of 30 children (26.7%), and 6 out of 31 children (19.4%), respectively. In those cases, the residual kyphosis inevitably developed. In the remaining children, the discs were intact or partially damaged. Among the 101 children kyphotic deformity was maintained without change in 20 children (19.8%). Kyphosis decreased in 14 children (13.9%), while it increased in 67 children (66.3%) with non-recoverably damaged growth plate. CONCLUSION: Although it is tentatively possible to predict the deformity progress or non-progress and spontaneous correction at the time of the initial treatment, its predictive accuracy is low. Therefore, assessment of the chronological changes should be performed at the end of chemotherapy. In children with progressive curve change, assessment of deformity should be continued until maturity.

Radiographic Assessment of Effect of Congenital Monosegment Synostosis of Lower Cervical Spine between C2-C6 on Adjacent Mobile Segments

STUDY DESIGN: A prospective radiographic study of cervical spine with congenital monosegment fusion. PURPOSE: To evaluate the effect of cervical synostosis on adjacent segments and the vertebral morphology. OVERVIEW OF LITERATURE: There are numerous clinical studies of adjacent segment disease (ASD) after monosegment surgical fusion. However, there was no report on ASD in the cervical spine with congenital monosegment synostosis. METHODS: Radiograms of 52 patients, aged 5 to 90 years, with congenital monosegment synostosis (CMS) between C2 and C6, who complained of neck/shoulder discomfort or pain were studied. 51 were normally aligned and one was kyphotically aligned. RESULTS: Spondylosis was not found in the patients below 35 years of age. Only 12 out of 24 patients with normally aligned C2-3 synostosis had spondylosis in 19 more caudal segments, and only one at C3-4. A patient with kyphotic C2-3 had spondylolysis at C3-4. In 8 patients with C3-4 synostosis, spondylosis was found in only 9 caudal segments (4 at C4-5, 4 at C5-6, and 1 at C6-7). The caudate C4-5 disc was the most liable to degenerate in comparison with other caudate segments. Caudal corporal flaring and inwaisting of the synostotic vertebra were the features that were the most evident. In 2 of 9 C4-5 and 7 out of 10 C5-6 synostosis patients, spondylosis was found at the two adjacent cephalad and caudate segments, respectively. Only corporal inwaisting without flaring was found. In all cases, spondylosis was confined to the adjacent segments. More advanced spondylosis was found in the immediate caudal segment than the cephalad one. CONCLUSIONS: It is concluded that spondylosis at the mobile segments in a synostotic spine is thought to be a fusion-related pathology rather than solely age-related disc degeneration. Those data suggested that CMS definitely precipitated the disc degeneration in the adjacent segments.

Surgery-Related Complications and Sequelae in Management of Tuberculosis of Spine

STUDY DESIGN: Medical record-based survey. PURPOSE: To survey the overall incidence of the intra- and postoperative complications and sequelae, and to propose the preventive measures to reduce complications in the spinal tuberculosis surgery. OVERVIEW OF LITERATURE: There is no study focused on the surgery-related complications and sequelae, with some touching lightly on the clinical problems. METHODS: There were 901 patients in this study, including 92 paraplegics. One hundred eighty-six patients had no visible deformity, while those of 715 patients were visible. Six hundred fifty-nine patients had slight to moderate non-rigid kyphosis, and 56 had severe rigid kyphosis. Sixty-seven out of 92 paraplegics had slight to moderate non-rigid kyphosis, and 25 had severe kyphosis. There were 134 cervical and cervicodorsal lesions, 518 thoracic and thoracolumbar lesions, and 249 lumbar and lumbosacral lesions. Seven hundred sixty-four patients had primarily anterior surgeries, and 137 had posterior surgeries. Instrumentation surgery was combined in 174 patients. RESULTS: There were intra- and postoperative complications: direct large vessel and neurological injuries (cord, roots, nerves), late thrombophlebitis, various thoracic cavity problems, esophagus and ureter injuries, peritoneum perforation, ileus, wound infections, stabilization failure, increase of deformity and late adjacent joint and bone problems. Thrombophlebitis and sympatheticolysis symptoms and signs in the lower limbs were the most common complications related with anterior lumbar and lumbosacral surgeries. Kyphosis increased in 31.5% of the non-instrumented anterior surgery cases (42% in children and 21% in adults). CONCLUSIONS: The safe, effective and most familiar surgical procedure should be adopted to minimize complications and sequelae. Cosmetic spinal surgery should be withheld if functional improvement could not be expected.

Preoperative Nutritional Status of the Surgical Patients in Jeju

BACKGROUND: To assess the preoperative nutritional status of patients with various disorders and to provide data for pre- and postoperative patient management plans, particularly in the elderly. There is no published information on age-matched and disease-matched preoperative nutritional/immunologic status for orthopedic patients, especially in the elderly, in Jeju. METHODS: In total, 331 patients with four categories of orthopedic conditions were assessed: 92 elective surgery patients, 59 arthroplasty patients, 145 patients with fractures, and 35 infection patients. Malnutrition was defined as body mass index (BMI) below 18 kg/m2 of expected body weight (below 20% of normal), serum albumin/globulin ratio below 1.5 (normal range, 1.5 to 2.3), albumin level below 3.5 g/dL, total lymphocyte count below 1,500 cells/mm3, and lymphocyte/monocyte ratio below 5 versus 1. RESULTS: In 92 elective surgery patients, the average BMI was 23 kg/m2, hemoglobin was 15 g/dL, lymphocytes (2,486 cells)/monocytes (465 cells) ratio was 6.1, and the albumin (4.4 g/dL)/globulin (2.5 g/dL) ratio as a protein quotient was 1.7. Among the 59 hip and knee arthroplasty patients, the average BMI was 25 kg/m2, hemoglobin was 12 g/dL, lymphocytes (2,038 cells)/monocytes (391 cells) ratio was 6.6, and albumin (4.1 g/dL)/globulin (2.4 g/dL) ratio was 1.6. No subject showed malnutrition. Among the 145 fracture patients, the average BMI was 23 kg/m2. The hemoglobin level was 13 g/dL, monocytes (495 cells)/lymphocytes (1,905 cells) ratio was 1 versus 4.6, and albumin (4.1 d/gL)/globulin (2.5 d/gL) ratio was 1.6. However, both ratios decreased after 70 years of age. Among the 17 of 35 infection patients, albumin levels were below 3.5 g/dL, the average BMI was 22 kg/m2, lymphocytes (1,532 cells)/monocytes (545 cells) ratio was 2.4 versus 1, and albumin (3.0 g/dL)/globulin (3.3 g/dL) ratio was 0.9, while in 18 patients albumin levels were over 3.5 g/dL, the average BMI was 22 kg/m2, hemoglobin was 12 g/dL, lymphocytes (1,998 cells)/monocytes (583 cells) ratio was 3 versus 1, and albumin/globulin ratio was 1.4. Thus, in the infection group, approximately 50% of the patients showed poor nutrition and immunosuppression. CONCLUSIONS: It was found that nutritional and immune condition deteriorated gradually to some degree in elderly patients over 60 years of age.

Randomized, Multi-center Phase II Trial of Docetaxel Plus Cisplatin Versus Etoposide Plus Cisplatin as the First-line Therapy for Patients with Advanced Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We prospectively conducted a multi-center, open-label, randomized phase II trial to compare the efficacy and safety of docetaxel plus cisplatin (DC) and etoposide plus cisplatin (EC) for treating advanced stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Seventy-eight previously untreated patients with locally advanced, recurrent or metastatic NSCLC were enrolled in this study. The patients received cisplatin 75 mg/m2 on day 1 and either docetaxel 75 mg/m2 on day 1 or etoposide 100 mg/m2 on days 1 to 3 in the DC or EC arm, respectively, every 3 weeks. RESULTS: The objective response rate was 39.4% (15/38) and 18.4% (7/38) (p=0.023) in the DC and EC arms, respectively. The median time to progression (TTP) was 5.9 and 2.7 months (p=0.119), and the overall survival was 12.1 and 8.7 months (p=0.168) in the DC and EC arms, respectively. The prognostic factors for longer survival were an earlier disease stage (stage III, p=0.0095), the responders to DC (p=0.0174) and the adenocarcinoma histology (p=0.0454). The grades 3 and 4 toxicities were similar in both arms, with more febrile neutropenia (7.9% vs. 0%) and fatigue (7.9% vs. 0%) being noted in the DC arm. CONCLUSION: DC offered a superior overall response rate than does EC, along with tolerable toxicity profiles, although the DC drug combination did not show significantly improved survival and TTP.

The Evaluation of the Efficacy and the Safety of Docetaxel in Korean Breast Cancer Patients: through Post-Authori- zation Survey to Fulfill the Registrative Requirement / 한국유방암학회지

PURPOSE: Post-authorization survey(PAS) is a useful tool for obtainting wider range of data on the safety and efficacy of new drugs following their approval, as they can detect uncommon, unreported adverse events(AEs), which enables more attention to be directed to the practioners. Especially, the limited number of patients in oncology trial cannot usually give the actual incidence of AEs. METHODS: Since Nov. 1998, when docetaxel gained Korean approval in the treatment of breast cancer, a PAS to investigate its safety profiles has been conducted targeting more than 600 patients over 4 calendar years. RESULTS: Case report forms from 626 out of 646 patients were assessable for safety and 444 for efficacy. The patient characteristics are: mean age, 48.1 years; male/female 4/622; Wt/Ht/BSA 57.9 kg/156.1 cm/1.56 m2 ; stage I-II/III/IV 109 (18.2%)/125 (20.8%)/366(61.0%). In 344 patients, 960 AEs were reported in severity of mild/moderate/severe in 6.7, 40.9 and 51.1 % of cases. From AE results, 36.0% needed dose reduction; 34.3% transient interruption of the cycle; and 1.3% permanent discontinuation of docetaxel. Thirty five serious AEs such as febrile neutropenia, alopecia, diarrhea, abdominal pain and headache were reported in 21 patients. Unexpected AEs such as skin ulcer, discoloration of skin, H. Zoster infection, ulticaria, facial flush, chest pain, hemoptysis, pneumonia, stridor, nasal bleeding, photophobia, haematuria, Cushing's syndrome, hyperglycemia and insomnia were reported regardless of any causal relationship. Factors affecting the development of AEs were age, stage, concomitant medication other than chemotherapeutic agents and the number of cycles treated. The efficacy was evaluable in 444 patients with overall response rate of 36.5% (CR/PR 6.3/30.2%). Factors affecting the efficacy were stage, concommitant medication other than chemotherapeutic agents and the number of treatment cycles. CONCLUSION: This post-authorization survey on the safety and efficacy of docetaxel in breast cancer offers oncology practice in the real world without subject selection as is the case in clinical trials, although it was performed to fulfill the registrative requirement of the Korean health authority with limited data. The efficacy and safety profile of docetaxel in breast cancer was no much different from those reported in clinical trials.

Correlation between Serum p53 Antibody and Tissue Expression of Mutant p53 Protein in Primary Breast Carcinoma Patients

PURPOSE: It has been reported that the antibody against p53 is detected in a certain proportion of patients with malignancies. The authors designed this study to investigate the correlation between appea rance of the serum p53 antibody and tissue expression of the mutant p53 protein in primary breast carcinomas. METHODS: We conducted assays for the serum p53 antibody in 76 patients with primary breast cancer by using a sandwich enzyme linked immunosorbent assay (ELISA). Immunohistochemical assays for tissue expression of the p53 mutant protein were also undertaken in the same patients, and the results were analyzed according to the patients' outcomes and the clinical/histopathologic parameters. RESULTS: Antibody against p53 was detected as a high titer in the sera of 12 patients (16.9%) whereas the mutant p53 protein was detected in 41.1% of the breast cancer tissues. We found a significant correlation between serum p53 antibody status and tissue expression of the mutant p53 protein (p=0.019), whereas serum p53 antibody status did not correlate with any clinical/histopathologic parameters except the histologic grade of the tumors. The antibody against the p53 protein was more frequently detected in the patients with undifferentiated tumors. In the survival analysis, the serum p53 antibody had no significant correlation with recurrence of the disease or with patient survival. CONCLUSION: It seems likely that accumulation of p53 protein in tumor cells may induce an immune response with the appearance of p53 antibodies in the sera of cancer patients. However, serum p53 antibody status failed to discriminate high risk population of breast cancer patients.

Behenoyl cytarabine-associated reversible encephalopathy in a patient with acute myelogenous leukemia

We report a case of reversible encephalopathy syndrome in a 16-year-old girl with acute myelogenous leukemia (AML), who is undergoing during consolidation chemotherapy composed of BH-AC (N4-behenoyl-1-beta-D-arabinofuranosyl cytosine) and idarubicin. On the 6th day of chemotherapy, she was in a drowsy state following generalized tonic clonic seizure lasting 20 minutes. MR images revealed extensive cortical and subcortical white matter brain edema. Alertness returned over the 24 hr following by the discontinuation of BH-AC and intravenous administration of diphenylhydantoin, although she complained of intermittent headaches and visual disturbance. She gradually recovered from these symptoms during subsequent 7 days. Previously noted abnormal signal intensities have nearly disappreared on follow-up MRI obtained on the 22nd day after the first seizure. She was discharged without any neurologic sequela. This case suggests that BH-AC, a derivative of cytosine arabinoside (1-beta-D-arabinofuranosylcytosine) could be a cause of reversible encephalopathy syndrome.

Comparison of Tropisetron with Ondansetron in the Prevention of Cisplatin-induced Nausea and Vomiting / 대한암학회지

PURPOSE: Tropisetron (Nabovan (R)) is a new specific 5-HT3 receptor antagonist with a long terminal half life in plasma and high bioavailability after oral intake. We compared the antiemetic effectiveness and tolerability of tropisetron with ondansetron in the highly emetogenic chemotherapy (including cisplatin > or =50 mg/m2). MATERIALS AND METHODS: Thirty-nine patients were administered in a randomized, multicenter, open, cross-over study and received either tropisetron plus dexamethasone (n=31) or ondansetron plus dexamethasone (n=34) during six days of two successive cycles of chemotherapy. RESULTS: Total control of vomiting with either Ondansetron or tropisetron was 94.2 % vs 93.5 % in D1 (P=0.157); 90.6 % vs 93.1 % in D2 (P=0.18); 90.3 % vs 93.1 % in D3 (P=0.655); 96.4% vs 96.4 % in D4 (P=0.157); 96.4 % vs 100 % in D5 (P=0.317); 96.4 % vs 100% in D6, respectively. The duration of nausea showed significant decreasements in tropisetron at D5 and D6 (P=0.025, P=0.03, respectively), but the severity of nausea and performance status showed no significance. Headache and constipation were the most common side effects in both groups. CONCLUSION: There was no significant difference in efficacy and tolerability between tropisetron and ondansetron in the cisplatin-based chemotherapy.

Etoposide, adriamycin and cisplatin(EAP) chemotherapy in advanced gastric cancer / 대한암학회지

No abstract available.