An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Systemic Sclerosis Associated with Non-small Cell Lung Cancer and Papillary Thyroid Cancer: Case Report and Literature Review / 대한내과학회지

We report the case of a 52-year-old patient with rheumatic vascular disease (systemic sclerosis), non-small cell lung cancer, and papillary thyroid cancer. Malignant tumors have been described in 3-11% of systemic sclerosis cases. Several studies have demonstrated an increased frequency of cancer, especially lung and breast cancer, in patients with systemic sclerosis, but the association of systemic sclerosis with malignancy is controversial. To our knowledge, however, no case of both lung and thyroid cancer associated with systemic sclerosis has been reported. We present a rare case of double primary cancer in systemic sclerosis, with a literature review.

Pleural Epithelioid Hemangioendothelioma

Epithelioid hemangioendothelioma (EHE) is a rare tumor of vascular origin. While it can be found in any tissue, it is most often found in lung and liver and usually has an intermediate behavior. EHEs originating from pleural tissue have been less frequently described than those from other sites. Furthermore, to date, all of the cited pleural EHEs were described as highly aggressive. In the present report, we describe a rare case of pleural EHE extending to lung and bone in a 31-year-old woman. The histological diagnosis was confirmed by both conventional examination and immunohistochemistry. Her disease stabilized during the 4th course of adriamycin (45mg/m2, day 1-3), dacarbazine (300mg/m2, day 1-3) and ifosfamide (2,500mg/m2, day 1-3) with mesna, and she survived for 10 months after the diagnosis.

A Case of Successful Intrapleural Chemotherapy with Cisplatin Plus Cytarabine for Intractable Malignant Pleural Effusion

When conventional treatments of malignant pleural effusion, such as repeated thoracentesis, closed thoracotomy and pleurodesis by instilled sclerosing agents, are ineffective, there are few alternative therapies available. Our case involves a 47-year-old woman with uterine cervical carcinoma suffering from malignant pleural effusion. She presented with a chief complaint of severe dyspnea, and was classified as an Eastern Cooperative Oncology Group (ECOG) performance status of 4. Her underlying cervical carcinoma progressed despite various systemic chemotherapy regimens. In addition, pleural effusion persisted in spite of 4 weeks of drainage through the thoracotomy tube and talc pleurodesis. Under such circumstances, we attempted intrapleural chemotherapy with cisplatin plus cytarabine, which resulted in significant decrease of the pleural effusion. No serious systemic toxicities, including myelosuppression, were observed. As a result, the patient's dyspnea was relieved, and her ECOG performance status improved from 4 to 2. However, the thoracotomy tube was not removed due to subsequent iatrogenic pneumothorax. Pleural effusion did not recur for the 4 weeks leading up to her death.

Pathological Analysis of Tumor Response after Preoperative Chemoradiation Therapy for Advanced Rectal Cancer

PURPOSE: We investigated the association of survivin expression with the prognosis in advanced rectal cancer with preoperative chemoradiotherapy for pathological analysis. METHODS: We examined 16 patients with rectal cancer who were preoperatively staged as T3 or T4. The enrolled patients were given 5-FU, 425 mg/m2/day, and leucovorin, 20 mg/m2/day, intravenously for 3 days during weeks 1 and 5 of pelvic radiotherapy. Surgical resection was performed 4~6 weeks after completion of the schedule. Tumor response was divided into CR (complete remission), PR (partial remission), and NR (non remission). Immunohistochemical staining of paraffin sections using monoclonal antibodies for survivin, bcl-2, and p53 was performed on pretreatment biopsy and surgically resected tissue by using the standard avidin-biotin-peroxidase technique. RESULTS: No CR was achieved. PR was achieved in 10 patients (62.5%), and NR in 6 patients (37.5%). After preoperative treatment, survivin expression tended to be decreased in tumor cells (62.5% to 31.3%) and slightly increased in adjacent normal mucosa a (12.5% to 25%). After preoperative treatment, survivin expression was correlated with lymph-node metastasis in the statistical analysis. We failed to find any other significant relationship between survivin expression and any parameters, except lymph node metastasis and apoptotic index. CONCLUSIONS: Survivin expression before preoperative treatment was not related to the prognosis in rectal cancer patients, but survivin expression after preoperative treatment was related to lymph node metastasis of advanced rectal cancer. Further studies, including large numbers of rectal cancer cases with a sufficient follow-up period, are needed in order to establish survivin as a prognostic target in rectal cancer.

Lemierre Syndrome: A Case of Postanginal Sepsis

Lemierre syndrome is a rare disease that's characterized by internal jugular vein thrombosis and septic emboli. These symptoms typically develop after acute oropharyngeal infection by Fusobacterium necrophorum1). Although this syndrome is less frequently seen in modern times due to the availability of antibiotics, physicians must be aware of the syndrome in order to initiate prompt antibiotics therapy, including coverage of the anerobic organisms. We discuss here the case of an 18-year-old female with Lemierre syndrome and we review the relevant literature on this syndrome.

Radiotherapy of Brain Metastases from Lung Cancer

PURPOSE : Brain metastasis is estimated to occur in 10~45% of solid cancer patients, and is the most common intracranial tumor in adults. Several neurologic symptom palliations are made with steroid therapy and whole brain irradiation. MATERIALS AND METHODS : We evaluated respectively the clinical characteristics and treatment outcome for 44 patients with metastatic brain tumor from lung cancer during the period from April 2000 to December 2003. RESULTS : Median age of the patients was 61 years. The male : female ratio was 2.7 : 1. Synchronous and metachronous brain metastasis was seen in 18 (40.9%) and 26 patients (59.1%), respectively and median duration between the diagnosis of lung cancer and brain metastases was 6 months (range 1~18 months) in metachronous cases. Pathologic types of lung cancer were as follows : small cell lung cancer in 11 patients and non-small cell lung cancer in 33 patients (squamous cell carcinoma-13, adenocarcinoma-11, large cell carcinoma- 3, others-6). The most common symptom of brain metastasis was headache, which was in 27 patients (61.4%). Seven patients (15.9%) had a single brain metastasis while 37 patients (84.1%) had multiple brain metastases. The total radiation dose to whole brain ranged from 30 to 40 Gy (median 30 Gy). In 29 patients (65.9%) neurological symptoms were resolved after whole brain irradiation. Median survival was 18 weeks for patients with steroid therapy and whole brain radiotherapy. CONCLUSION : In present study, we confirmed that whole brain irradiation is an effective palliative treatment for patients with metastatic brain tumors from lung cancer

Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non-Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies. MATERIALS AND METHODS: Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks. RESULTS: Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed. CONCLUSION: The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.

Infusional 5-Fluorouracil, Leucovorin and Docetaxel in Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was performed to estimate the response rate and toxicity of a combination chemotherapy, which included infusional 5-Fluorouracil, Leucovorin and Docetaxel in the treatment of patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Twenty two advanced gastric cancer patients, with a bidimensionally measurable or an evaluable disease, were enrolled in this study. The patients received a 5-fluorouracil 1, 000 mg/m2 intravenous (IV) 24 hour infusion (Day 1~3), leucovorin 20 mg/m2 (Day 1~3) and docetaxel 75 mg/m2 intravenously (Day 2) every 3 weeks. RESULTS: The overall response rate was 45.0%. The median duration of response was 10.0 weeks (range: 4~24), the median time to response was 8 weeks (range: 8~20) the median time to progression was 30.0 weeks (95% CI: 16.3~43.2) and the median overall survival duration was 36.0 weeks (95% CI: 1.7~70.2). The median cumulative dose of 5-fluorouracil were 316.2 mg/m2/week and docetaxel was 23.9 mg/m2/week. WHO grade III, IV neutropenia, thromocytopenia and anemia occurred in 50.0%, 4.5% and 4.5% of patients, respectively. There were no occurrence of WHO grade III and IV nausea, vomiting, mucositis, conspitation, diarrhea, or neurotoxicity. CONCLUSION: This chemotherapy regimen, including infusional 5-fluorouracil, leucovorin and docetaxel was an active agent against advanced gastric cancer patients, especially for previous chemotherapy naive patients.

A Case of Paraneoplastic Nephrotic Syndrome in a Patient with Ovarian Carcinoma

Nephrotic syndrome is a rare manifestation of malignancy associated with paraneoplastic syndrome. Paraneoplastic nephrotic syndrome has been reported in various malignancies: malignant lymphoma, colon cancer, lung cancer and prostate cancer. However, an ovarian carcinoma associated with nephrotic syndrome has rarely been reported. Only six cases of ovarian carcinoma associated paraneoplastic nephrotic syndrome has been reported worldwide, but no cases have been reported in Korea. Here, we report a case of paraneoplastic nephrotic syndrome in a patient with an ovarian carcinoma. The patient presented with ascites, proteinuria and hypoalbuminemia. An initial computed tomography (CT) scan and ultrasonography evaluations showed no specific findings suggestive of an ovarian tumor. Despite treatment for nephrotic syndrome, the symptoms became more aggravated. There after, follow up evaluation at Yonsei University Medical Center, including serum CA 125, pelvis MRI and peritoneal fluid examination were performed. On the pelvis MRI, a left ovarian mass was detected with an ascitic fluid collection. The serum CA 125 level was elevated to 2211 U/ml. The peritoneal fluid cytological examination showed malignant cells suggestive of an ovarian carcinoma. Combination chemotherapies including paclitaxel plus carboplatin, topotecan plus gemcitabine and oxaliplatin plus capecitabine were administered to the patient, and complete remission was achieved on image and tumor marker studies. There was complete recovery from the nephrotic syndrome with no evidence of ascites and proteinuria. These findings suggest that nephrotic syndrome caused by paraneoplastic syndrome can be resolved only after the complete control of the underlying malignancy.

The Effect of ZD 1839 (Iressa(R)) in the Treatment of Refractory Non Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to evaluate the efficacy and the safety of ZD 1839 (Iressa(R)) as a 3rd or 4th line chemotherapy regimen in NSCLC patients who are refractory to a previous chemotherapy regimen. MATERIALS AND METHODS: Twenty-five patients who were refractory to previous chemotherapy were selected for this study. The eligible patients had an ECOG performance status of 0 to 2, and an appropriate end organ function. ZD 1839 (Iressa(R))250 mg/d was orally administered until the patients experienced disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were analyzed. The median age of the patients was 57 years. The response rate was 12.0% with partial responses in 3 patients. Fourteen patients (56%) remained in the stable disease state and 8 patients progressed. The median overall survival was 9.0 months (95% CI 6.7~11.2). The median progression free survival was 3 months (95% CI 2.2~3.8). Hematological toxicities of grade 3 or 4 neutropenia, anemia and thrombocytopenia were absent. Non-hematological toxicities were grade 2 or 3 skin rashes in 10 (40.0%) patients and 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients. No patient failed to continue chemotherapy due to any drug-related adverse events. CONCLUSION: The results suggest that ZD 1839 (Iressa(R)) monotherapy is effective and tolerable as a 3rd or 4th line salvage treatment for NSCLC patients refractory to previous chemotherapy regimens.

Paclitaxel and Cisplatin Combination Chemotherapy in Pretreated Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A single institute trial of combination chemotherapy, with paclitaxel and cisplatin, in patients with metastatic breast cancer, having failed previous combination chemotherapy, was performed. MATERIALS AND METHODS: Patients were only eligible for this study if there disease had progressed, following treatment with previous chemotherapy, in either an adjuvant or a metastatic setting. Paclitaxel 175 mg/m2 was administered as a 3-hour continuous infusion on day 1, and cisplatin 80 mg/m2 was administered for 2 hours on day 2, with adequate hydration. This was repeated every 3 weeks, and continued until one of the following events occurred: disease progression, unacceptable adverse effect or treatment refusal by the patient. Intercurrent palliative radiotherapy, or concurrent hormonal therapy, was permitted, depending on each patient's status. All the endpoints were evaluated under the principle of intention to treat analysis. RESULTS: A total of 24 patients entered the study, and 18 had at least one measurable lesion, but 6 did not. The objective response rate of the 18 patients was 50%(9/18). Two were complete responses and seven showed partial responses. The median response duration, progression free and overall survival were 5.3 months (range, 4~18), 6 months (95% CI, 5~7) and 12 months (95% CI, 7~17), respectively. 67% of the planned dose was administered. Out of a total 135 cycles administered, about 20% of cycles showed grade 3 or 4 leukopenia and 7% showed grade 3 thrombocytopenia. Two patients suffered from pneumonia, and one experienced neutropenic fever. Mucositis, greater than grade 3, existed in three cases. No treatment related deaths were reported. CONCLUSION: The combination chemotherapy, with paclitaxel and cisplatin, was active in the treatment of metastatic breast cancer patients having failed previous chemotherapy.

Efficacy of Chronic Oral Etoposide and Tamoxifen in the Far-Advanced Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: This study evaluated the use and efficacy of chronic oral etoposide plus tamoxifen as a palliative treatment in 30 patients with far-advanced HCC in whom surgical resection, percutaneous ethanol injection or transarterial chemoembolization(TACE) was not possible. METHODS: To be eligible for the study, patients had to have objectively measurable or evaluable tumors, adequate hematologic profiles and hepatorenal functions, had to be between 20 and 75 years of age, and had to have an ECOG performance status of less than or equal to 2. The treatment included etoposide, 50 mg/m2/day, taken orally for 21 days, and tamoxifen, 40 mg/day, taken orally for 21 days. Each cycle was repeated every 5 weeks. RESULTS: Two patients(7%) achieved a partial response(PR) and 16 patients(53%) achieved a stable disease(SD) with a median time-to-progression of 5 months(range: 2-24). Median of patients survival with the response of PR or SD and those patients with the response of progressive disease(PD) was 10 months and 7 months, respectively(p=0.0004). Of the 20 patients with initial elevated serum alpha-fetoprotein(> or =500 ng/ml), 9 patients(45%) experienced a significant(> or =50%) decrease in their values after chemotherapy and all 9 patients achieved objective tumor response of more than or equal to SD. Among the 30 patients in the study, 10 patients(33%) achieved performance status improvements of grade according to the ECOG criteria and 6 patients(20%) experienced improvements of subjective symptoms, such as abdominal pain, abdominal fullness and anorexia. CONCLUSION: Based on our results, the use of chronic oral etoposide plus tamoxifen as a palliative treatment for the far-advanced hepatocellular carcinoma are beneficial. A randomized two-arm study may be warranted to validate the results of this study.

A Case of Remitting Seronegative Symmetrical Synovitis with Pitting Edema(RS3PE) Syndrome / 대한류마티스학회지

RS3PE is used to describe patients who have peripheral seronegative polyarthritis and pitting edema, especially in a man older than 60. It is characterized by sudden onset, high sedimentation rate, lack of bony erosion, remission within 18 months and good prognosis. Whether the RS3PE is a unique disease or syndrome has long been discussed, but conclusion was not obtained. We describe a 72 year old man of RS3PE with a review of the literature.

The Value of PSA as a Molecular Predictor of Bony Metastasis in Prostatic Cancer / 대한비뇨기과학회지

To evaluate the correlation between serum PSA(prostate specific antigen) levels and bone metastasis and to identify better criteria for the selection of appropriate candidates for bone scan, we reviewed the medical records of 53 patients with prostatic adenocarcinoma who were managed at Seoul National University Hospital from January 1990 to December 1993. PSA was measured by monoclonal radioimmunometric assay.(ELSA PSA) Histologic grade, tumor stage as well as status of metastasis were compared with the level of PSA. We stratified bony lesions which were evaluated with bone scan into extent of disease(EOD). The PSA level increased as tumor stage increased but this was not statistically significant. There was positive correlation between the PSA level and Gleason sum. The mean value of PSA in the group of non-metastasis was 106.2ng/ml compared to 711.8ng/ml in the group with metastasis. This was statistically significant. There was no correlation between the PSA level and extent of disease but PSA levels of EOD 1 group was significantly lower than those of remaining group. When we stratified patients with bony metastasis according to the PSA level, only 1 of 13 patients with PSA of 20ng/ml or less had bony metastasis. Its negative predictive value was 92.3%. In conclusion, patients with PSA of 20ng/ml or less are not likely to have bony metastasis. Further large-scaled prospective study is needed to determine the predictability of PSA for bony metastases more accurately.

A Case of Transitional Medulloblastoma in the Posterior Fossa of a Child

The case is reported of a 2 1/2-year-old femal with headache, vomiting and paraparesis. Clinical feature and operative findings are quite different from those of classic medulloblastoma in its lateral location, well-circumscribed tendency, non-invasiveness, no CSF metastasis, and favourable prognosis after surgical removal. Histological features are the combination of those of classic, and desmoplastic medulloblastoma. Review of literature was done.

Wide-Spread Benign Schwannoma Involving Multiple Cervical Vertebral Bodies

Benign Schwannoma rarely involves the vertebral bodies extensively. Two cases of widespread involvement of cervical vertebral bodies by Schwannoma are reported. Despite of huge amount of neoplastic mass and severe destructive bony changes, the neurologic deficits were minimal and postoperative result was not discouraging. Finding of plain X-rays, cervical CT scan and tumor pathology were discussed as well as surgical approach.