Although concurrent chemoradiotherapy (CCRT) has been considered as a standard treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN), this treament is associated with increased toxicities such as mucositis and dermatitis. As a result, the dose intensity can be reduced and interruptions of radiotherapy are more common for CCRT than for sequential treatment, especially for the elderly patients. This prospective study was performed to assess the efficacy and safety profiles of the induction chemotherapy of docetaxel and cisplatin for elderly patients with locally advanced SCCHN.
Patients over 65 years of age with locally advanced SCCHN were treated with docetaxel (70 mg/m2) and cisplatin (75 mg/m2) every 21 days. The chemotherapy consisted of two cycles with a third cycle that was administered to the responding patients. Patients who did not respond to initial chemotherapy underwent radiotherapy as a definitive local treatment.
Fifty patients were enrolled in this study and 44 patients were assessable for response and toxicity. The overall response rate was 88%, 16 patients (36%) achieved a complete response and 23 patients (52%) achieved a partial response. After a median follow-up of 24 months (range: 9~38 months) the median disease free period and overall survival period had not yet been reached. The one year and two year survival rates were 89% and 70%, respectively. The most common grade 3/4 adverse event was neutropenia, which occurred in 33 patients (75%) and 4 patients had febrile neutropenia.
Combination chemotherapy of docetaxel and cisplatin is an effective regimen with an acceptable safety profile as the induction treatment for elderly patients suffering with SCCHN.
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To evaluate the therapeutic activity and safety of paclitaxel and cisplatin combination chemotherapy in patients with advanced or metastatic gastric cancers that are unresponsive to primary chemotherapy.
Advanced or metastatic gastric cancer patients unresponsive to first line chemotherapy were entered into this trial. The treatment regimen consisted of paclitaxel, 175 mg/m2 by 3-hour infusion on day 1, and cisplatin, 60 mg/m2 by 1 hour infusion on day 1, with the treatment repeated every 3 weeks.
37 patients were entered in this study, with 32 fully evaluable for response. 4 (13%), 13 (40%) and 15 (47%) patients achieved a partial response, stable disease and progressed, respectively. The median time to progression was 4.0 months (95% CI: 2.0~6.0 months), and the median overall survival was 12.6 months (95% CI: 5.5~19.7 months), with a 1-year survival rate of 54%. Of a total of 135 cycles of chemotherapy, grades 3 and 4 hematological toxicities were neutropenia (14%) and anemia (3%). Grade ≥2 neuropathy was observed in 6 patients (17%).
The combination of paclitaxel and cisplatin is an effective and tolerable salvage treatment modality for advanced gastric cancer.
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Anatomy of deep pelvis, narrow distal margin and tumor invasion into neighbor organ are obstacles for curative radical resection for advanced cancer of distal rectum. Technically, laparoscopic application after downstaging the tumor with preoperative concurrent chemotherapy (CCRT) may give a solution to overcome the anatomical difficulties. We compared the results of laparoscopic surgery in the patients who received CCRT with those of patients who had conventional surgery.
A continuous infusion of 5FU plus leucovorin and radiotherapy (50.4 Gy) in 28 fractions was given each patient as CCRT. They underwent D2 radical resection with TME and ANP for the rectal cancer in 4 weeks.
Thirty three patients had laparoscopic resection such as LAR, colo-anal anastomosis and APR. The results were compared with 12 cases of the conventional resections. As a result of preoperative CCRT, the cancer was down-staged in 71%. Two year disease free survival was 75% and 74% in the group of conventional and laparoscopic resection, respectively (p=0.427). Ileus, voiding difficulty and leakage after surgery were not different between two groups. Weakness of ejaculation was noted in 9~11% of both groups. The DFS of the preoperative CCRT followed by radical resection in the groups with a response was more favorable than that in the group with progressive or stable disease.
Radical resection of advanced distal rectal cancer could be done with performing a laparoscopic assisted operation after CCRT induced down-staging. We may suggest that laparoscopic assisted resection is a good treatment option as it doesn't increase the complications and it has a compatible survival rate to conventional surgery.
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Although radiation-induced necrosis (RIN) is not a tumor in itself, the lesion progressively enlarges with mass effects and diffuse peritumoral edema in a way that resembles neoplasm. To identify the RIN that mimics progression of brain metastasis, we performed surgical resections of symptomatic RIN lesions.
From June 2003 to December 2005, 7 patients received stereotactic-guided radiotherapy (SRT) for metastatic brain tumor, and they later underwent craniotomy and tumor resection due to the progressive mass effects and the peritumoral edema that caused focal neurological deficit. On MR imaging, a ring-like enhanced single lesion with massive peritumoral edema could not be distinguished from progression of brain metastasis.
Four patients had non-small cell lung cancer, 2 patients had colorectal cancer and 1 patient had renal cell carcinoma. The mean tumor volume was 8.7 ml (range: 3.0~20.7 ml). The prescribed dose of SRT was 30 Gy with 4 fractions for one patient, 18 Gy for two patients and 20 Gy for the other four patients. The four patients who received SRT with a dose of 20 Gy had RIN with or without microscopic residual tumor cells.
Early detection of recurrent disease after radiotherapy and identifying radiation-induced tissue damage are important for delivering adequate treatment. Therefore, specific diagnostic tools that can distinguish RIN from progression of metastatic brain tumor need to be developed.
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We investigated the mechanism by which some types of cancer cells grow faster in the presence of ascorbic acid supplementation.
Adj.PC-5, a mouse plasmacytoma cell, is known to show ascorbic acid-dependent growth and was chosen as a test system. The growth of cancer cells was measured by the colony number on soft agar or the cellular proliferation in suspension culture. The ascorbate level was measured by a high performance liquid chromatography system with an electrochemical detector. Glucose 6-phosphate dehydrogenase was analyzed both on the specific enzyme activity level and on the transcription level by performing Northern blot analysis.
Ascorbyl 2-phosphate among the ascorbate derivatives was the most efficient in stimulating cell growth. The intracellular and extracellular ascorbate concentrations following treatment with either ascorbate or ascorbyl 2-phosphate suggest that the superiority of ascorbyl 2-phosphate for stimulating cell growth may be due to its slow conversion to ascorbate in the culture medium. The steady transformation to ascorbate ensures sustained levels of ascorbate in the culture medium and thereby maximizes the growth stimulatory effect of ascorbate. Ascorbyl 2-phosphate markedly enhanced, in a concentration-and time-dependent manner, mRNA synthesis as well as the enzymatic activity of glucose 6-phosphate dehydrogenase, which is known to be a rate-limiting enzyme in cell growth. On the other hand, simultaneous addition of dehydroisoandrosterone, a well- known inhibitor of glucose 6-phosphate dehydrogenase, to the culture medium abrogated the growth stimulation by ascorbyl 2-phosphate, and it also reduced the glucose 6-phosphate dehydrogenase activity proportionately.
The results from this study suggest that enhanced glucose 6-phosphate dehydrogenase activity may at least in part explain the stimulation of cell growth by ascorbate or ascorbyl 2-phosphate.
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Recent studies have shown that Dickkopf-1 (DKK-1) is overexpressed in some tumors, including hepatocellular carcinoma. However, the role of increased DKK-1 in these tumors is not known. In this study, the DKK-1 expression in hepatocellular carcinoma (HCC) cell lines was evaluated and the effect of DKK-1 overexpression in HCC cell lines was studied.
The expression of DKK-1 in hepatocellular carcinoma cell lines was evaluated by RT-PCR. Stable cell lines that overexpressed DKK-1 were established. Cell growth, adhesion, migration and invasion assays were performed.
RT-PCR analysis showed that 5 out of 8 HCC cell lines expressed DKK-1. The forced expression of DKK-1 suppressed the growth of cells and increased the population of cells in the sub-G1 phase. In addition, DKK-1 reduced the cellular adhesion capacity to collagen type I and fibronectin, and it increased migratory capacity. However, overexpression of DKK-1 did not increase the invasion capacity of the HCC cell line.
Collectively, our data suggest that overexpression of DKK-1 affects the biology of HCC cells.
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A patient with adenocarcinoma of the lung was treated sequentially using two kinds of EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. The patient was a 73-year-old female who received gefitinib as a second line treatment, which resulted in a partial response with response duration of 6 months. After progression of the disease, the patient received erlotinib, which resulted in partial response again with response duration of 11.5 months. This observation suggests that treatment with erlotinib may be effective in patients who develop progressive disease after a primary treatment with gefitinib following an initial response.
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A 43-year-old male presented with a painless left testicular mass. The pathologic diagnosis of the radical orchiectomy specimen was peripheral T-cell lymphoma, unspecified (PTCL-u). According to the Ann Arbor staging system, his initial stage was III because of the right nasopharyngeal involvement. After first-line chemotherapy with four courses of the CHOP regimen and this was followed by involved-field radiotherapy, he achieved complete remission. Two months later, disease recurred to the left ciliary body of the left eye without evidence of involvement at other sites. Although the patient received intensive chemotherapy with autologous hematopoietic stem cell transplantation, he ultimately died of leptomeningeal seeding. Because both the central nervous system (CNS) and the orbit are sanctuary sites for chemotherapy, orbital infiltration of lymphoma should prompt physicians to evaluate involvement of the CNS and to consider performing prophylactic intrathecal chemotherapy as a treatment option.
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