A Randomized Phase II Trial of Capecitabine Plus Vinorelbine Followed by Docetaxel Versus Adriamycin Plus Cyclophosphamide Followed by Docetaxel as Neoadjuvant Chemotherapy for Breast Cancer.

PURPOSE: Given the promising activity of capecitabine and vinorelbine in metastatic breast cancer, this randomized phase II trial evaluated the efficacy and safety of this combination as neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Patients with operable breast cancer (n=75) were randomly assigned to receive either four cycles of adriamycin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks followed by four cycles of docetaxel 75 mg/m(2) every 3 weeks (AC-D) or four cycles of capecitabine 2,000 mg/m(2) (day 1-14) plus vinorelbine 25 mg/m(2) (days 1 and 8) every 3 weeks followed by four cycles of docetaxel 75 mg/m(2) (CV-D). The primary endpoint was pathologic complete response (pCR) in the primary breast (ypT0/is). RESULTS: Most patients (84%) had locally advanced (n=41) or inflammatory breast cancer (n=22). pCR rates in the primary breast were 15% (95% confidence interval [CI], 7% to 30%) and 11% (95% CI, 4% to 26%) in the AC-D and CV-D groups, respectively. The overall response rates and 5-year progression-free survival rates in the AC-D and CV-D groups were 62% and 64%, and 51.3% (95% CI, 34.6% to 68.0%) and 30.2% (95% CI, 13.3% to 47.1%), respectively. Although both regimens were well tolerated, CV-D showed less frequent grade 3-4 neutropenia and vomiting than AC-D, whereas manageable diarrhea and hand-foot syndrome were more common in the CV-D group. CONCLUSION: CV-D is a feasible and active non-anthracycline-based neoadjuvant chemotherapy regimen for breast cancer.

Superior mesenteric vein thrombosis as an early presentation of myelodysplastic syndrome: a case report.

Mesenteric venous thrombosis (MVT) is a serious condition due to its potential association with mesenteric ischemia and infarction of the small bowel. Symptoms of MVT are often vague, making accurate diagnosis and sufficient treatment difficult. However, increased awareness and new imaging modalities for this condition have improved outcomes for patients with MVT. Treatment includes anticoagulation, transcatheter therapy, and surgery. In the present report, we describe the case study of a 62-year-old woman with a presenting diagnosis of superior MVT, who was finally diagnosed with myelodysplastic syndrome. The superior MVT spontaneously dissolved after the patient underwent 6 months of systemic anticoagulation therapy. Invasive surgery or bowel resection was not required.

Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer treatment.

Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week.

Primary anaplastic large cell lymphoma of the lung presenting with acute atelectasis.

Non-Hodgkin lymphoma only rarely occurs as a primary lung mass. We report a very rare case of primary pulmonary anaplastic large cell lymphoma presenting with acute atelectasis in a 55-year-old man. Chest computed tomography revealed a consolidated central mass in the left lung with obstructive pneumonia that had developed into total atelectasis. After a bronchoscopic examination failed to yield a definite diagnosis, supraclavicular lymph node biopsy was performed, revealing an anaplastic large cell lymphoma. This case illustrates the need for rapidly locating a possible biopsy site, other than the primary lung mass itself, and the value of empirical steroid treatment for avoiding devastating exacerbation when aggressive pulmonary lymphoma is suspected.

Small cell carcinoma of the liver and biliary tract without jaundice.

An 80-year-old woman presenting with chest pain was found to have a large, lobulated soft tissue mass in the liver and nearby tissues on abdominal computed tomography (CT). The tumor had invaded the common hepatic artery and main portal vein. Jaundice developed 4 wk later, at which point, a pancreas and biliary CT scan revealed a large mass in the right lobe of the liver and a hilar duct obstruction, which was found to be a small cell carcinoma. Despite its rarity, liver and bile duct small cell carcinoma should be considered in the differential diagnosis of atypical chest pain without jaundice.

Solitary rectal metastasis from primary small cell lung carcinoma.

Lung cancer may rarely appear with a solitary rectal metastasis and no other metastases. We report the first case of primary small cell lung cancer presenting with a solitary rectal metastasis in a 62-year-old man. Chest computed tomography revealed a soft tissue lesion in the subcarinal area. Following bronchoscopic biopsy, the patient was diagnosed with small cell lung cancer. The rectal mass was incidentally found during an imaging study for staging work-up. Histological examination revealed that the rectal mass was consistent with metastasis from small cell lung cancer. We suggest that clinicians should consider the possibility of rectal metastasis in small cell lung cancer patients with rectal masses.

Randomized trial of postoperative adjuvant therapy in Stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: 10-year follow-up.

PURPOSE: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. METHODS AND MATERIALS: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m(2)/day and leucovorin 20 mg/m(2)/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. RESULTS: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). CONCLUSIONS: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

Brain metastases in breast cancer: prognostic factors and management.

BACKGROUND: The purpose of this retrospective study was to analyze the overall survival of patients with brain metastases due to breast cancer and to identify prognostic factors that affect clinical outcome. METHODS: Of the 7,872 breast cancer patients histologically diagnosed with breast cancer between January 1990 and July 2006 at the Asan Medical Center, 198 patients with solitary or multiple brain metastases were included in this retrospective study. Central nervous system (CNS) lesions were diagnosed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients with leptomeningeal or dural metastases without co-existent parenchymal metastatic lesions were excluded in this study. We reviewed the medical records and pathologic data of these 198 patients to characterize the clinical features and outcomes. RESULTS: The median age of the patients at the diagnosis of brain metastases was 45 years (range 26-78 years). Fifty-five patients (28%) had a single brain metastasis, whereas 143 (72%) had more than two metastases. A total of 157 (79.2%) patients received whole-brain radiation therapy (WBRT). A total of 7 (3.6%) patients underwent resection of solitary brain metastases, 22 (11%) patients underwent gamma-knife surgery, three patients underwent intrathecal chemotherapy (1.5%) and 9 (4.6%) patients received no treatment. The overall median survival time was 5.6 months (95% confidence interval (CI), 4.7-6.5 months) and 23.1% of the patients survived for more than 1 year. The median overall survival time was 5.4 months for patients treated with WBRT, 14.9 months for patients treated with surgery or gamma-knife surgery only, and 2.1 months for patients who received no treatment (P < 0.001). Multivariate analysis demonstrated that Eastern Cooperative Oncology Group (ECOG) performance status (relative risk (RR) = 0.704, 95% CI 0.482-1.028, P = 0.069), number of brain metastases (RR = 0.682, 95% CI 0.459-1.014, P = 0.058), treatment modalities (RR = 1.686, 95% CI 1.022-2.781, P = 0.041), and systemic chemotherapy after brain metastases (RR = 1.871, 95% CI 1.353-2.586, P < 0.001) were independent factors associated with survival. CONCLUSION: Although survival of breast cancer patients with brain metastases was generally short, the performance status, number of brain metastases, treatment modalities and systemic chemotherapy after brain metastases were significantly associated with survival. Patients with single-brain metastasis and good performance status deserve aggressive treatment. The characteristics of initial primary breast lesions did not affect survival after brain metastasis.

Extrapulmonary small cell carcinoma: single center experience with 61 patients.

Extrapulmonary small-cell carcinoma (EPSCC) is a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. The aim of this study was to review the clinico-pathologic features, treatment modalities, and factors prognostic for survival in patients with EPSCC. We retrospectively reviewed the medical records of patients with EPSCC diagnosed between January 1995 and July 2004 at the Asan Medical Center. We identified 61 patients with EPSCC, 37 with limited disease (LD) and 24 with extensive disease (ED). The most common primary sites were the gastrointestinal (GI) tract (56%) and uterine cervix (18%). Overall survival (OS) at 1 and 3 years was 59% and 29%, respectively, with a median survival of 16 months (range, 1 approximately 56 months). Treatment information was available for 51 patients, 34 with LD and 17 with ED. Of the 34 LD patients, 25 underwent surgery. Surgery was the only treatment modality in five patients, two of whom remained alive and disease free at last follow-up, 27 and 47 months after surgery, respectively. Adjuvant chemoradiotherapy was administered to 11 patients, nine of whom (82%) had distant failure with a median overall survival of 23 months. Of the eight patients who received adjuvant chemotherapy, four (50%) had distant failure, with a median survival of 21.7 months. In univariate analysis, advanced disease status, as measured by VALSG (LD vs. ED) stage, was a significant prognostic factor for OS (p<0.001). Interestingly, there were no statistically significant differences in progression-free survival or OS between patients with pure (n=45) and mixed (n=16) EPSCC. Overall, the response to various treatment modalities and the median survival time observed were discouraging. Patients with GI primary tumors had poorer prognoses than those with primary tumors at other locations. Fifty six percent of patients with a GI primary tumor had ED at the time of diagnosis, whereas 100% of patients with SCC of the uterine cervix had LD at the time of diagnosis and showed a favorable clinical course. The majority of patients with LD SCC who underwent surgery, followed by adjuvant chemotherapy or chemoradiotherapy, showed tumor recurrence and/or systemic metastases. Clinical trials are needed to define adequate treatment strategies for EPSCC.

Intramedullary spinal cord metastases: a single-institution experience.

BACKGROUND: Intramedullary spinal cord metastasis (ISCM) is the rarest type of CNS involvement of systemic malignant tumors. The aim of this retrospective study is to evaluate the clinical features, treatment and natural course of patients with ISCM in a single institution of Korea. METHODS: We reviewed the medical records of all patients diagnosed with secondary malignant neoplasms involving the spinal cord at the Asan Medical Center between January 1995 and August 2006. Patients were diagnosed with ISCM if they had pathologically established malignancies originating outside the central nervous system (CNS), neurologic symptoms suggestive of spinal cord dysfunction, and either abnormal spinal MRI findings suggestive of ISCM or surgical or postmortem confirmation of ISCM. We excluded patients in whom ISCM was suspected because of known cancer and myelopathy, but with normal neuroimaging results. RESULTS: All 12 ISCMs arised from breast cancer (six patients) and lung cancer (three small cell lung cancer, three non-small cell lung cancer). Eight lesions were in the thoracic cord, one in the cervical cord, and three in both. In 11 patients, brain metastasis were combined with the development of ISCM. Initial symptoms included various paresthesias, sensory loss, and leg weakness. The duration of symptoms before diagnosis ranged from 2 days to 8 months (median, 7 days). Despite radiotherapy, neurologic status usually deteriorated rapidly, within a period of days to weeks. Median survival after ISCM diagnosis was 3.9 months (range 0.8-18.4 months) for all patients (breast cancer 5.5 months vs. lung cancer 1.0 month). CONCLUSION: Our findings indicate that ISCM is a very rare type of CNS involvement and represents a dismal finding of systemic malignancy. ISCM patients arising from breast cancer appeared to fare better than those with lung cancer.

Combination chemotherapy with capecitabine (X) and Cisplatin (P) as first line treatment in advanced gastric cancer: experience of 223 patients with prognostic factor analysis.

BACKGROUND: The efficacy and safety of the combination of capecitabine (X) and cisplatin (P) in the treatment of advanced gastric cancer (AGC) have already been shown in several prospective clinical trials. In this study, we sought to evaluate the efficacy and feasibility of the XP combination for the treatment of AGC in clinical practice and to determine the prognostic factors affecting treatment outcomes. METHODS: Clinical data from 223 patients with previously untreated metastatic, unresectable, or recurrent gastric carcinoma who were treated with XP between March 2000 and December 2004 at a single center were reviewed. Each 3-week chemotherapy cycle consisted of oral capecitabine (1000-1250 mg/m2 twice a day on days 1-14) and i.v. cisplatin (60-80 mg/m2 on day 1). RESULTS: Of the 223 patients, 32 had distant metastases but palliative gastrectomy (resected metastatic), 82 had recurrent disease after previous curative gastrectomy (recurrent), and 109 had distant metastases without gastrectomy (initially metastatic). Patients received a median of five cycles of chemotherapy (range, 1-12 cycles). Among the 123 patients with measurable disease, seven achieved complete responses and 49 had partial responses, giving an overall response rate (RR) of 45.5% in the intention-to-treat population (95% CI, 32.9-50.2%). There were no differences in RR among the groups of resected metastatic, recurrent and initially metastatic patients (66.7 versus 36.5 versus 50.8%, P = 0.35). After a median follow-up of 11.9 months (range, 2.1-51.9 months), the median time to progression (TTP) was 6.3 months (95% CI, 5.2-7.4 months) and the median overall survival (OS) was 11.1 months (95% CI, 9.4-12.9 months). In the resected metastatic, recurrent and initially metastatic groups, TTP was 8.7, 6.8 and 5.8 months (P = 0.02) and median OS was 14.7, 12.4 and 9.6 months (P = 0.03), respectively. Multivariate analysis showed that relatively small tumor burden (resected metastatic or recurrent versus initially metastatic groups) (OR = 1.418, 95% CI, 1.021-1.967, P = 0.037) and good performance status (ECOG 0-1 versus 2) (OR = 3.800, 95% CI, 2.417-5.974, P < 0.001) were independent prognostic factors affecting overall survival. CONCLUSION: The combination of capecitabine and cisplatin was active and well tolerated as a first line treatment of AGC in general clinical practice. Disease status and performance status of the patients were the most important factors in treatment outcomes.

Hepatitis B reactivation during adjuvant anthracycline-based chemotherapy in patients with breast cancer: a single institution's experience.

BACKGROUND: The objectives of this study were to determine the incidence, outcome and risk factors for HBV reactivation in HBsAg positive breast cancer patients while on anthracycline -based adjuvant chemotherapy. METHODS: We retrospectively reviewed the records of 2,431 patients with early breast cancer who received adjuvant chemotherapy from March 2001 to December 2005. Among these patients, 111 HBsAg positive women were enrolled in this study. RESULTS: Thirty-seven patients (33.3%) developed acute hepatitis, of which 23 (20.7%) were related to HBV reactivation. Univariate analysis showed that an age > or = 7 years (p 0 .034) and abnormal sonographic findings such as a fatty liver or cirrhotic changes (p= 0 .034) were associated with HBV reactivation. However, an HBeAg positive status and the use of corticosteroids were not. Multivariate analysis found that no clinical factors could predict HBV reactivation during chemotherapy. All 23 patients who developed HBV reactivation received lamivudine as a therapeutic measure at the time of HBV reactivation. Despite the use of lamivudine, disruption in the chemotherapy protocol occurred in 18 patients (78.3%) and 14 of these patients had premature termination of their chemotherapy. CONCLUSIONS: HBV reactivation occurred in a significant proportion of HBsAg positive patients during adjuvant anthracycline-based chemotherapy. Once hepatitis developed, most patients could not finish the chemotherapy as planned despite lamivudine treatment. Until the risk factors for reactivation are clearly identified, HbsAg-positive patients should begin prophylactic antiviral treatment before initiating chemotherapy.

A case of leukemic pleural infiltration in atypical chronic myeloid leukemia.

Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely reported in the literature. When the pleural effusion is caused by leukemic pleural infiltration, the differential white blood cell count of the effusion is identical to that of the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone marrow examination, chromosome analysis and polymerase chain reaction he was diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages of granulocytes and a few blasts were present in both the pleural fluid and a peripheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.

Treatment-induced menstrual changes in very young (<35 years old) breast cancer patients.

PURPOSE: To evaluate the treatment-induced menstrual changes in very young (< 35 years old) breast cancer patients. METHODS AND MATERIALS: We retrospectively examined the clinical records of 160 patients, ranging in age from 18 to 34 years old (median age, 32 years), treated between June 1992 and December 2002. One hundred twenty patients underwent mastectomy and 40 underwent breast conserving surgery. Postoperatively, 80 patients were treated with alkylating agent-based chemotherapy regimens (CMF) and 80 with anthracycline-based regimens (AD). In addition, 57 patients received adjuvant radiotherapy, and 77 received anti-estrogen therapy. Treatment-induced menstrual changes and present menstrual status were evaluated from hospital records and by one-to-one interviews. The median follow-up period was 54 months (range, 29-156 months). RESULTS: Treatment-induced menstrual change (amenorrhea) was occurred in 59 (36.9%) patients, 25 (31.3%) of those treated with CMF and 34 (42.5%) with AD (p=0.142). Amenorrhea occurred after a median 2 cycles of chemotherapy (range, 1-6 cycles). Menstruation resumed in 49 (83.1%) patients, 20 (80%) of those treated with CMF and 29 (85.3%) with AD (p=0.6). Median time to resumption of menstruation was median 3.5 months (range, 1-18 months) after amenorrhea. Disease recurred in 10 (16.9%) patients who experienced treatment-induced menstrual changes and in 18 (17.8%) of those who did not (p=0.89). CONCLUSION: Although the overall incidence of treatment-induced menstrual change in breast cancer patients under age 35 was similar to that reported elsewhere, the rate of recovery from these change is higher. We observed no difference between CMF and AD treated patients in rates of amenorrhea or recovery from these changes.

Continuous infusion intermediate-dose cytarabine, mitoxantrone, plus etoposide for refractory or early relapsed acute myelogenous leukemia.

For refractory and early relapsed AML, this prospective phase II clinical trial evaluated a salvage chemotherapy regimen, which was consisted of continuous infusion intermediate-dose cytarabine (1g/m(2)/day, 24h i.v. infusion x 5), mitoxantrone (12 mg/m(2)/day x 3), and etoposide (150 mg/m(2)/day x 3). We treated 33 patients and 17 (51.5%) achieved CR with a median duration of 117 days. Median overall survival was 219 days. Our results suggest that continuous infusion intermediate-dose cytarabine, together with mitoxantrone and etoposide, may induce CR in a significant proportion of patients with refractory or early relapsed AML, although remission duration was short.

Gemcitabine single or combination chemotherapy in post anthracycline and taxane salvage treatment of metastatic breast cancer: retrospective analysis of 124 patients.

PURPOSE: To evaluate the efficacy of gemcitabine-based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2(nd)-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and gemcitabine/capecitabine (GX). MATERIALS AND METHODS: Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively. RESULTS: The median number of prior metastatic chemotherapy regimens was 2 (range 0 approximately 4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5 approximately 9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0 approximately 4.2 months). Compared with monotherapy (G), combination therapy with vinorelbine or capecitabine (GV/GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival. CONCLUSIONS: The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2(nd)-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

Prognostic factors identifiable at the time of onset of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Current grading systems of acute graft-versus-host disease (GVHD) cannot effectively identify patients with poor prognosis at the onset of acute GVHD after allogeneic hematopoietic cell transplantation. DESIGN AND METHODS: In a retrospective analysis, we evaluated the prognostic value of various clinical parameters at the initiation of treatment in 83 patients who developed systemic treatment-requiring acute GVHD after allogeneic hematopoietic cell transplantation. RESULTS: Forty-three of 83 patients (52%) experienced initial treatment failure (40 required secondary treatment due to lack of response and 3 died) and 43 (52%) experienced treatment success, defined as completion of treatment (initial and, if given, secondary) within 100 days. The GVHD-specific survival rate was 65.5%, with 27 deaths due to GVHD-related complications without relapse of underlying malignancies within 1 year. HLA-mismatched transplantation, visceral initiation, and peripheral blood lymphocytopenia ( pound100/mL) were independent variables predicting higher initial treatment failure (Odd ratios (OR)=12.225, 12.036, and 7.481, respectively). The above variables and initial acute GVHD grade III-IV vs. II were independent variables predicting shorter GVHD-specific survival (OR=0.322, 0.247, 0.340, and 0.385, respectively). High-risk disease status, visceral initiation, and hypoalbuminemia ( pound2.8 g/dL) were independent variables predicting lower treatment success (OR=0.221, 0.162, and 0.270, respectively). The predictive value of visceral initiation and lymphocytopenia for GVHD-specific survival was verified in an independent cohort of 58 patients. INTERPRETATION AND CONCLUSIONS: Lymphocytopenia and hypoalbuminemia may be useful baseline prognostic factors for acute GVHD after allogeneic hematopoietic cell transplantation.

Docetaxel plus epirubicin as first-line chemotherapy in MBC (KCSG 01-10-05): phase II trial and the predictive values of circulating HER2 extracellular domain and vascular endothelial growth factor.

The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer (MBC). We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospective assessment of the predictive values of circulating HER2 extracellular domain (ECD) and vascular endothelial growth factor (VEGF). Docetaxel 75 mg/m(2) and epirubicin 75 mg/m(2) were given intravenously every 3 weeks. Prophylactic G-CSF was not used. Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay. Forty MBC patients were enrolled, and 39 patients were evaluable for toxicities and 38 for response. Complete response was observed in 3 (7.9%) patients, partial response in 20 (52.6%) (overall response rate 60.5%), stable disease in 11 (28.9%) and disease progression in 4 (10.5%). After a median follow-up of 22.5 months, the median duration of response was 28 weeks, median time to disease progression was 32 weeks, and median survival was 15.8 months. Two-hundred and fifteen cycles of treatment were administered (median, 6 cycles per patient). Grade 3 and 4 neutropenia were observed during 24 (11.2%) and 74 (35%) cycles respectively, and grade 3 or 4 febrile neutropenia in 24 (11.2%) cycles. Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration (p<0.005) and shorter time to progression (p<0.005). However, elevated VEGF levels were not found to be correlated with response rate or survival. We concluded that the docetaxel and epirubicin combination is an effective first-line treatment in MBC patients and that elevated serum HER2 ECD levels, but not circulating VEGF levels, predict a poor outcome.

Phase II study of paclitaxel and carboplatin in advanced gastric cancer previously treated with 5-fluorouracil and platinum.

BACKGROUND: The combination of paclitaxel and carboplatin has been used to treat patients with many types of tumor, including gastric cancer. We evaluated the efficacy and safety of this combination in advanced gastric cancer patients previously treated with 5-fluorouracil and platinum. METHODS: Patients who had pathologically been proven to have measurable lesions were treated with paclitaxel (200 mg/m(2) for 3 h) and carboplatin [area under the concentration-time curve (AUC = 6)] on day 1 and in 21 day cycles. RESULTS: A partial response was achieved in 10 of 45 patients [22%, 95% confidence interval (CI), 10-34]. Of the 32 patients previously treated with cisplatin, four (13%) achieved partial response, whereas, of the 13 patients previously treated with heptaplatin, six (46%) achieved partial response. In all patients, the median time to progression was 14 weeks (95% CI, 10-18), and the median overall survival was 32 weeks (95% CI, 26-38). The most common grade 3/4 adverse events were neutropenia (40% of patients) and neuropathy (2.2%). Two patients developed neutropenic fever. However, there were no treatment-related deaths. CONCLUSIONS: Combination chemotherapy with paclitaxel and carboplatin is feasible in patients with advanced gastric cancer who were previously treated with 5-fluorouracil and platinum.

High-dose chemotherapy of cyclophosphamide, thiotepa and carboplatin (CTCb) followed by autologous stem-cell transplantation as a consolidation for breast cancer patients with 10 or more positive lymph nodes: a 5-year follow-up results.

PURPOSE: The benefit of consolidation high-dose chemotherapy (HDC) for high-risk primary breast cancer is controversial. We evaluated the efficacy and safety of consolidation HDC with cyclophosphamide, thiotepa and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) in resected breast cancer patients with 10 or more positive lymph nodes. MATERIALS AND METHODS: Between December 1994 and April 2000, 22 patients were enrolled. All patients received 2 to 6 cycles of adjuvant chemotherapy after surgery for breast cancer. The HDC regimen consisted of cyclophosphamide 1,500 mg/m(2)/day, thiotepa 125 mg/m(2)/day and carboplatin 200 mg/m(2)/day intravenous for 4 consecutive days. RESULTS: With a median follow-up of 58 months, 11 patients recurred and died. The median disease-free survival (DFS) and median overall survival (OS) were 49 and 69 months, respectively. The 5-year DFS and OS rates were 50% and 58%, respectively. The 12 patients with 10 to 18 involved nodes had better 5-year DFS (67%) and OS (75%) than 10 patients with more than 18 involved nodes (30% and 38%, respectively). The most common grade 3 or 4 nonhematologic toxicity was diarrhea, which occurred in 5 patients (23%). No treatment-related death was observed. CONCLUSION: Consolidation HDC with CTCb followed by ASCT for resected breast cancer with more than 10 positive nodes had an acceptable toxicity but does not show promising survival.