No abstract available.
Carcinoma, Non-Small-Cell Lung* ; Drug Therapy* ; Hope*

PURPOSE: We investigated the effectiveness and safety of DA-3030 for prophylatic use in patients receiving chemotherapy for malignant disease. MATERIALS AND METHODS: Seventy cancer patients were randomized to receive chemotherapy alone (36 patients) or with DA-3030 administered (34 patients) after stratified block randomization according to chemotherapeutic regimen. DA-3030 was subcutaneously administered at the dose of 100 pg/m/day for 10 days from 24 hours after the completion of chemotherapy. RESULTS: Of the 70 enrolled patients, 62 patients were evaluable. The neutropenia (absolute neutrophil count [ANC] <1,000/mm) occurred in 9 of 32 (28.1%) of the DA-3030 group and 21 of 30 (90.0%) of the control group, giving relative risk for control group of 0.154 (95% confidence interval [CI], 0.05 to 0.45; p-0.0001). Severe neutropenia (ANC 500/mm') occurred in 4 of 32 (12.5%) of the DA-3030 group and in 20 of 30 (66.7%) of the control group (relative risk for control group of 0.316 [95% CI, 0,18 to 0.55]; p=0.0001). The mean duration of neutropenic period (+/-standard error) was 1.13+/-0.34 days in the DA-3030 group and 6.73+/-0.69 days in the control group respectively, and was significantly shorter in the DA-3030 group (p<0.0001). And, there was higher nadir ANC in the OA-3030 group than that in the control group (p=0.0001); the mean nadir ANC was 2,547+/- 343/mm and 442+/-120/mm, respectively. The DA-3030 group had significantly higher incidence of myalgia in comparison to the control group (43.8% compared with 3.3%; p=0.001). However, it was tolerable and was easily managed by conservative therapy CONCLUSION: The use of DA-3030 was effective in preventing chemotherapy-induced neutropenia.
Drug Therapy* ; Humans ; Incidence ; Myalgia ; Neutropenia* ; Neutrophils ; Random Allocation

The clinical outcome and prognostic factors of patients with synchronous brain metastases from non-small cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKS) were analyzed. A total of 35 patients with NSCLC underwent GKS as an initial treatment for metastatic brain lesions of synchronous onset. The period of survival and various prognostic factors such as age, gender, performance status, multiplicity of the brain lesions, intracranial tumor volume, and extent of the primary tumor were analyzed. The overall median survival time for this series was 12 months (range 0.75 to 43 months) from the diagnosis. Of the 21 patients who were no longer alive at the conclusion of this study, only 7 (33.3%) died of neurological causes. Multivariate analysis of these data revealed that N stage, whole-brain radiotherapy (WBRT), and chemotherapy were significant predictors for survival (p<0.05). Survival of patients with NSCLC and synchronous brain metastases is mainly dependent upon the progression of the systemic disease, provided that the cerebral lesions are treated adequately with local treatment modalities including radiosurgery. Application of radiosurgery as an initial treatment option and aggressive local and systemic modalities to control extracranial disease may improve survival.
Treatment Outcome ; Time Factors ; Radiosurgery/*methods ; Prognosis ; Neoplasm Metastasis ; Middle Aged ; Male ; Lung Neoplasms/*diagnosis/pathology/*surgery ; Humans ; Female ; Carcinoma, Non-Small-Cell Lung/*diagnosis/pathology/*surgery ; Brain Neoplasms/*diagnosis/pathology/*surgery ; Aged, 80 and over ; Aged ; Adult

Primary malignant melanoma arising in a cystic teratoma of ovary is extremely rare. Approximately 25 cases of primary malignant melanoma arising from a cystic teratoma in ovary have been reported in the literature. The malignant transformation of benign cystic teratoma of ovary usually develops unilaterally in postmenopausal women. The common presenting symptoms are abdominal distention, lower abdominal pain and a palpable abdominal mass. We report a case of primary malignant melanoma of ovary in a 45-year-old patient who underwent laparotomy for evaluation of a cystic mass in right ovarian cystic teratoma. Histopathological examination of the cyst showed that it was melanoma with pre-existed teratomatous components. Extraovarian primary site was not found. Nine years after the excision, brain metastases developed which were pathologically confirmed as metastatic melanoma. The patient subsequently developed pulmonary metastases and received immunochemotherapy consisting of cisplatin, dacarbazine, vinblastine, interleukin-2 and interferone-alpha. She is on a regular follow-up and continues to have stable disease for 9 months.
Abdominal Pain ; Brain ; Cisplatin ; Dacarbazine ; Female ; Follow-Up Studies ; Humans ; Interleukin-2 ; Laparotomy ; Melanoma* ; Middle Aged ; Neoplasm Metastasis ; Ovarian Cysts ; Ovarian Neoplasms ; Ovary ; Teratoma* ; Vinblastine

Cytokine has been used as an immune stimulator and administered to patients for a treatment of cancer. Interleukin-12 (IL-12) is a potent cytokine which acts through a variety of functions including interferon-gamma production and cytotoxic T-cell activation. Considering the toxicity of high dose systemic IL-12 administration into human, local administration of low dose IL-12 can be a more efficient strategy. In ex vivo therapy, human dermal fibroblast has been considered as a useful vehicle for transferring genes, Here we show that human dermal fibroblast transduced with retrovirus containing IL-12 gene can be manipulated to produce reasonable amount of IL-12 protein. Human dermal fibroblast was isolated from freshly harvested skin specimens by collagenase digestion, grown in primary cultures, and transduced with a retroviral vector containing genes for human IL-12 and a selectable marker Neo(R). Following selection in G418, IL-12 producing fibroblasts were tested for secreted IL-12 level by ELISA. Six specimens of human skin were processed to obtain fibroblasts. ELISA results show that 40-150 units of IL-12 was produced for 24 h from 1x10(6) cells of transduced and selected fibroblast cultures. The primary cultures were maintained for up to nine passages about 108 days. The mean +/- overall time for obtaining enough number of cells was 49 +/- 2 days. The fibroblasts continued to produce IL-12 in culture for 90 days. These preliminary results can be used for the design of ex vivo gene therapy clinical trial using human dermal fibroblast.
Collagenases ; Digestion ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts* ; Genes, Neoplasm* ; Genetic Therapy ; Humans* ; Interferon-gamma ; Interleukin-12* ; Retroviridae ; Skin ; T-Lymphocytes ; Zidovudine

PURPOSE: A novel chemically modified heparin derivative, heparin-deoxycholic acid nano-particles, has lower anticoagulant activity, and was recently reported to have significant anti-tumor effects on squamous head and neck cancer cells. Therefore, the aim of this study was to evaluate the anti-tumor effects of heparin-deoxycholic acid nano-particles in a human lung adenocarcinoma cell line. MATERIALS AND METHODS: An orthotopic lung cancer model in 16 mice was developed using intra-thoracic injections of 0.5x10(6) PC14PE6 cells. Ten days after inoculation, the mice were divided into two groups. PBS and Heparin-DOCA particles were injected once a day every 3 days in the tail vein, for a total of 5 injections. The body weight and survival of each mouse were monitored and the tumor size in the lung was measured by SPECT-CT before and after heparin-DOCA nano-particle treatment. RESULTS: IThe HD particles had no significant cytotoxicity when the PC9 cells were treated in vitro. There was no statistical difference in tumor size, body weight and survival between the HD treated and control groups in vivo. Furthermore, there was no difference in the amount of CD31 between tumor tissues in the two study groups. CONCLUSION: HD synthesized with unfractionated heparin had no apparent inhibitory effects on tumor growth in a PC14PE6 cell induced orthotopic lung cancer mouse model. The HD particles did not significantly inhibit tumor-induced angiogenesis at the tumor sites.
Adenocarcinoma ; Animals ; Bile ; Body Size ; Body Weight ; Cell Line ; Head and Neck Neoplasms ; Heparin ; Humans ; Lung ; Lung Neoplasms ; Mice ; Veins

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors. METHODS: We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples. RESULTS: Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment. CONCLUSIONS: NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.
Adenocarcinoma* ; Biopsy ; Carcinoma, Non-Small-Cell Lung ; Female ; Humans ; Lung ; Lung Neoplasms ; Phenotype ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Small Cell Lung Carcinoma*

This is to examine whether aggressive multimodality therapy improves the treatment outcomes in stage IIIA non-small cell lung cancer (NSCLC). Fifty-three consecutive NSCLC patients with N2 disease, confirmed by mediastinoscopic biopsy, received preoperative thoracic radiation therapy (45 Gy/5 weeks) concurrent with two cycles of oral etoposide and intravenous cisplatin and surgery. Postoperative radiation therapy (PORT, 18 Gy/2 weeks) was optionally recommended for those with the risk factors of loco-regional recurrence based on the surgical and pathological findings. Surgical resection was performed in 38 patients (71.7%), and down-staging was achieved in 19 patients (50%). The median survival period was 27 months in 38 patients who underwent resection, and the rates at 3-yr of overall survival, loco-regional control, distant metastasis-free survival, and disease-free survival were 44.3%, 87.9%, 32.9%, and 29.3%. Significantly favorable factor regarding overall survival was achieving p0/I stage by the multivariate analysis. PORT was successful in reducing locoregional recurrences in patients with the risk factors. Current preoperative concurrent radiochemotherapy and surgery by the authors resulted in comparable survival with other reports, however, further refinement of multimodality approach may be warranted for more effective reduction of distant metastasis.
Treatment Failure ; Time Factors ; Survival Rate ; Prognosis ; Neoplasm Staging ; Middle Aged ; Male ; Lung Neoplasms/mortality/pathology/*therapy ; Humans ; Female ; Disease-Free Survival ; Combined Modality Therapy ; Carcinoma, Non-Small-Cell Lung/mortality/pathology/secondary/*therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Aged ; Adult

PURPOSE: To evaluate the prognostic implication of histopathologic findings on the surgical specimens of N2 positive stage IIIA non-small cell lung cancer (NSCLC) patients who were treated with preoperative concurrent radiochemotherapy (CRCT) and surgery. MATERIALS AND METHODS: From May 1997 to April 2000, 48 patients with N2 positive stage IIIA NSCLC were treated with preoperative CRCT and surgery. Retrospective analyses were performed on 33 patients who underwent surgical resection. The thoracic radiation therapy (TRT) dose was 45 Gy over 5 weeks with a 1.8 Gy daily fraction using 10 MV X-rays. Chemotherapy consisted of two cycles of intravenous cisplatin (100 mg/m2, on days 1 and 29) and oral etoposide (50 mg/m2/day, on days 1~14 and 29~42), concurrently delivered with TRT. Surgery was performed around 4 weeks of the completion of CRCT. The median follow up was 18 months. The histopathologic findings, including the proportions of viable tumor cells, fibrosis, and necrosis, as well as the tumor and nodal statuses on the surgical specimens following the preoperative CRCT, were analyzed. RESULTS: The 3-year overall survival, disease-free survival, and local control rates were 46.1%, 49.5%, and 85.5%, respectively. Post-surgical stages decreased in 18 patients (54.5%), including 3 pathologic complete responses, were unchanged in 13 (39.4%), and increased in two (6.1%). On univariate analyses, the low proportion of the viable tumor cells was the only factor favorably affecting the overall survival rate (p=0.0386), and the histologic type of squamous cell carcinoma was a favorable factor affecting disease free survival rate (p=0.0452). On multivariate analyses, however, no factor affected the overall survival, disease free survival, or local control rates. CONCLUSION: The histopathologic findings of the proportion of viable tumor cells, fibrosis, and necrosis on the surgical specimens following preoperative CRCT had few prognostic implications on uni-and multi-variate analyses. Furthermore, the primary tumor and nodal responses to preoperative CRCT did not influence the outcomes. Longer-term follow-up with a larger number of patients, however, is awaited.
Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Chemoradiotherapy* ; Cisplatin ; Disease-Free Survival ; Drug Therapy ; Etoposide ; Fibrosis ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Necrosis ; Retrospective Studies ; Survival Rate

BACKGROUND: Invasive aspergillosis is an important cause of morbidity and mortality in neutropenic patients after chemotherapy in hematologic malignancies. HEPA filtration was known as an effective preventive measure for invasive aspergillosis, but the role of chemoprophylaxis has not been established yet. Itraconazole has been considered to be an effective antifungal agent for invasive aspergillosis. We evaluated the effect of itraconazole chemoprophylaxis in the prevention of invasive aspergillosis for neutropenic patients after chemotherapy in hematologic malignancies, who were treated in general ward without HEPA filtration. METHODS: A total of 89 patients with hematologic malignancies were enrolled in the two groups between January, 1995 and December, 1997 at Samsung medical center. Itraconazole, 200 mg po twice daily, was given to the patients as their neutrophil count decreased below 1,000/microliter following chemotherapy, and continued until it recovered over 1,000/microliter. Incidence of invasive aspergillosis was prospectively compared between the itraconazole prophylaxis group and the control group. RESULTS: Itraconazole prophyaxis was done in 34 patients on a total 59 episodes of severe neutropenia (absolute neutrophil count <500/microliter) after chemotherapy. Two out of 34 patients were histologically diagnosed as invasive aspergillosis. Control group included 55 patients with 103 episodes of severe neutropenia. Five out of 55 patients were diagnosed as invasive aspergillosis. No statistically significant differences were observed between two groups, because 2 of 59 (3.4%) and 5 of 103 (4.9%) were found to have invasive aspergillosis proven histologically (P=1.00). CONCLUSION: Itraconazole chemoprophylaxis for invasive aspergillosis was not effective, and the prognosis was closely related to the recovery of neutrophils. But we cannot exclude thepossibility that the drug has been failed in achieving effective plasma concentration by oral administration, as reported in several studies. Randomized prospective study, including measurement of plasma drug concentration, is warranted to evaluate the efficacy of itraconazole for the prevention of invasive aspergillosis.
Administration, Oral ; Aspergillosis* ; Chemoprevention ; Drug Therapy ; Filtration ; Hematologic Neoplasms ; Humans ; Incidence ; Itraconazole* ; Mortality ; Neutropenia ; Neutrophils ; Patients' Rooms ; Plasma ; Prognosis ; Prospective Studies