A progressively rising level of serum prostate specific antigen (PSA) after radical prostatectomy (RP) invariably indicates the recurrence of prostate cancer. The optimal management of patients with post-RP PSA relapse has remained uncertain due to a wide variability in the natural course of post-RP PSA relapse and the inability to separate a recurrent disease confined to the prostate bed from that with occult distant metastasis. Management uncertainty is further compounded by the lack of phase III clinical studies demonstrating which therapeutic approach, if any, would prolong life with no significant morbidity. Radiotherapy has been the main therapeutic modality with a curative potential for patients with post-RP PSA relapse. This review article depicts issues and challenges in the management of patients with post-RP PSA relapse, presents the literature data for the efficacy of salvage radiotherapy, either alone or in combination of androgen ablation therapy, and discusses future directions that can optimize treatment strategies.
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To assess the efficacy and safety of treating Korean patients with metastatic hormone-refractory prostate cancer (HRPC) using docetaxel plus prednisolone chemotherapy.
This was a retrospective cohort study performed in 98 patients with metastatic HRPC between October 2003 and April 2008. After screening, 72 patients fit the eligibility criteria for inclusion in this study. Treatment consisted of 5 mg prednisolone twice daily and 75 mg/m2 docetaxel once every 3 weeks.
Patient demographic characteristics included: median age 67 years (range, 51~86), median ECOG performance status 1 (0~2), Gleason score ≥8 in 61 patients (86%), and median serum PSA 45.5 ng/mL (range, 3.7~2,420.0). A total of 405 cycles of treatment were administered with a median 6 cycles (range, 1~20) per patient. The median docetaxel dose-intensity was 24.4 mg/m2/week (range, 17.5~25.6). A PSA response was seen in 51% of 63 evaluable patients at 12 weeks and maximal PSA decline ≥50% in 59% of 70 evaluable patients. Tumor response was evaluated in 13 patients, 4 patients achieved PR, and 5 patients had SD with a response rate of 31%. With a median follow-up duration of 23.1 months (95%CI, 16.7~29.5), the median time to PSA progression was 5.1 months (95%CI, 4.5~5.8) and median overall survival was 22.8 months (95%CI, 16.6~29.1). Nine (13%) patients experienced grade 3 or higher febrile neutropenia.
This chemotherapy regimen (docetaxel every 3 weeks plus prednisolone daily) demonstrated a strong response in Korean patients with metastatic HRPC, while the toxicity profile was manageable and similar to that observed in Western patients.
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Treatment options for patients with advanced gastric cancer remain limited. Few studies have investigated the efficacy and tolerability of the combination regimen of oxaliplatin and 5-fluorouracil with leucovorin for patients with advanced gastric cancer. The goal of this study was to examine the efficacy and toxicity of a modified FOLFOX-6 (mFOLFOX-6) regimen as a first-line chemotherapy regimen for patients with advanced gastric cancer.
From March, 2006, to December, 2007, 82 patients with advanced gastric cancer received 100 mg/m2 oxaliplatin and 100 mg/m2 leucovorin on the first day of treatment, followed by 2,400 mg/m2 of 5-fluorouracil on the first and second days of treatment every 2 weeks as a first-line treatment.
The median age of the enrolled patients was 62 years (range; 30~75). Out of 82 patients, 34 cases (41.5%) were recurrent cases after curative resection, and the other 48 cases were unresectable or non-curative resectable cases. Their response was evaluated every 6 weeks. The overall response rate was 40.2%, with 2 (2.4%) complete response and 31 (37.8%) partial responses. The median time to progression (TTP) and overall survival (OS) time were 6.0 months (95% confidence interval [CI]: 4.69~7.31) and 13.0 months (7.99~18.0), respectively. The grade 3~4 hematologic toxicities observed included neutropenia (34.1%), thrombocytopenia (7.3%), and anemia (1.2%). The gastrointestinal toxicities observed included grade 3~4 nausea (9.8%) and vomiting (7.3%). Six patients (7.3%) experienced grade 3 neuropathy. No treatment-related deaths were recorded.
The modified FOLFOX-6 regimen is effective and well tolerated as a first-line chemotherapy regimen for patients with advanced gastric cancer.
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This study was designed to determine the efficacy and safety of FOLFOX-4 chemotherapy as a salvage treatment for patients with advanced gastric cancer (AGC).
The AGC patients with an ECOG performance status of 0~1 and progressive disease after prior treatments were registered onto this phase II trial. The patients received oxaliplatin (85 mg/m2 on day 1), leucovorin (200 mg/m2 on days 1 and 2) and 5-fluorouracil (400 mg/m2 as a bolus and 600 mg/m2 as a 22-hour infusion on days 1 and 2) every 2 weeks.
For the 42 treated patients, a total of 228 chemotherapy cycles (median: 5, range: 1~12) were administered. Twenty-nine patients (69%) received FOLFOX-4 chemotherapy as a third-(50%) or fourth-line (19%) treatment. On the intent-to-treat analysis, 9 patients (21%) achieved a partial response, which was maintained for 4.6 months. The median progression-free survival and overall survival were 3.0 months and 6.2 months, respectively. The frequently encountered toxicities were neutropenia and gastrointestinal side effects, including anorexia. Although there was one possible treatment-related death, the toxicity profiles were generally predictable and manageable.
Salvage chemotherapy with FOLFOX-4 is an effective and tolerable regimen for those heavily pretreated AGC patients who have a good performance status.
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We estimated the likelihood of breast cancer patients having axillary lymph node metastases (ALNM) based on a variety of clinical and pathologic factors.
Three hundred sixty-one breast cancer patients without distant metastases and who underwent breast conserving surgery and axillary lymph node dissection (ALND) (level I and II) or modified radical mastectomy (MRM) were identified, and we retrospectively reviewed their pathology records and treatment charts.
Positive axillary lymph nodes were detected in 104 patients for an overall incidence of 28.8%: 2 patients (5%) with T1a tumor, 5 (9.2%) with T1b tumor, 24 (21.8%) with T1c tumor and 73 (44.2%) with T2 tumor. On the multivariate analysis, an increased tumor size (adjusted OR=11.87, p=0.02), the presence of lymphovascular invasion (adjusted OR=7.41, p<0.01), a triple negative profile (ER/PR-, Her2-) (adjusted OR=2.09, p=0.04) and a palpable mass at the time of diagnosis (adjusted OR=2.31, p=0.03) were all significant independent factors for positive ALNM.
In our study, the tumor size, the presence of lymphovascular invasion, a triple negative profile and a palpable mass were the independent predictive factors for ALNM. The tumor size was the strongest predictor of ALNM. Thus, the exact estimation of the extent of tumor is necessary for clinicians to optimize the patients' care. Patients with a triple negative profile have a high incidence of ALNM irrespective of the tumor size.
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Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although
We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months.
Clinical responses were correlated with
Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by
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Maspin is a tumor suppressor protein that has been reported to stimulate the cell death of cancer and inhibit the metastasis of cancer. The present study aimed to explore the survival pathway by which maspin modulates the resistance of human lung cancer cells to chemotherapeutic drugs, and the consequences of maspin gene therapy in an animal model.
NCI-H157 and A549 cells were transfected with either a mock vector (pCMVTaq4C), maspin (pCMV-maspin), siControl or siMaspin. RT-PCR and Western blot analysis were performed to study the expressions of survival proteins in lung cancer. cDNA microarray analysis was carried out to compare the maspin-modulated gene expression between the xenograft tumors derived from the lung cancer cells that were stably transfected with pCMVTaq4C or pCMV-maspin. Maspin gene therapy was performed by intra-tumoral injections of pCMVTaq4C or pCMV-maspin into the pre-established subcutaneous tumors in nude mice.
Maspin significantly decreased the survival to doxorubicin and etoposide, whereas did not affect the survival to cisplatin in the NCI-H157 cells. Interestingly, transfection with a maspin plasmid resulted in a significant reduction of the phosphorylation of Akt in the NCI-H157 cells, whereas knockdown of maspin increased the phosphorylation of Akt in the A549 cells. Microarray analysis of the xenograft tumors revealed a specific gene expression profile, demonstrating that maspin is associated with the differential expressions of PTEN and IGF2R. Direct transfer of pCMV-maspin into the tumor significantly retarded the tumor growth in the animal experiments (p=0.0048).
Lung cancer cells lacking maspin could be resistant to chemotherapeutic drugs such as doxorubicin or etoposide, at least in part by maintaining Akt phosphorylation.
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Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Epidemiological studies have demonstrated an increased risk of subsequent cancer in the patients who are diagnosed with idiopathic venous thrombosis. Cancers of the breast, lung and ovary in women and adenocarcinomas of an unknown primary cancer are most strongly associated with thrombosis. Mucin-producing cancers are most often associated with VTE and the highest rates of VTE were found for cases of ovarian cancer, but the absolute risk of cancer after thrombosis is relatively low (about 2% over the first year) and so the benefit of screening for cancer in thrombosis patients seems limited. But as this case, the association between thrombosis and occult cancer shows the importance of this association for patients who have thrombosis that is unresponsive to anticoagulant therapy. Especially, we should recognize that such patients can undergo investigation for an underlying malignancy. Diagnostic laparoscopy of an adnexal mass for confirming cancer in the acute setting of deep vein thrombosis (DVT) was performed for our patient. We report here on a case of a patient with DVT in the upper and lower extremities before the diagnosis of ovarian cancer, and we briefly review of the relevant literature.
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Multiple primary cancers are the occurrence of more than two cancers of different origin in an individual. Penile cancer is a rare disease, and finding it combined with other cancers is even rarer. A 64-year-old man with a painful penile mass was referred to us from a primary urological clinic. We performed a biopsy of the penile mass and the histology revealed a well-differentiated squamous cell carcinoma. Abdominal computed tomography showed a localized bladder tumor with inguinal lymphadenopathy. The patient underwent a partial penectomy, transurethral resection of the bladder tumor and inguinal lymph node dissection. The histology of the bladder tumor was high-grade papillary carcinoma, and that of the lymph node was squamous cell carcinoma. The penile and bladder tumors were in stage II (T1N1M0) and stage I (T1N0M0), respectively. We successfully treated the patient with adjuvant radiotherapy and systemic chemotherapy.
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A dedifferentiated liposarcoma of the retroperitoneum is an extremely rare tumor. A 51-year old man was admitted to our department because a retroperitoneal mass was seen on abdominal computed tomography at another hospital. Computed tomography of the abdomen and magnetic resonance imaging showed a large pelvic mass located in the right hemipelvis, and it was pushing the right ureter and invading the right kidney, duodenum, colon and inferior vena cava. The patient underwent right radical nephrectomy, pylorus preserving pancreatoduodenectomy, right hemicolectomy and artificial blood vessel replacement for the inferior vena cava. The histopathological diagnosis was dedifferentiated liposarcoma and the patient was free from recurrence on the computed tomography that was done 6 months after the operation.
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