The aim of this study was to investigate the risk factors for dysphagia induced by chemoradiotherapy for head and neck cancers.
Forty-seven patients with head and neck cancers who underwent definitive chemoradiotherapy from December 1998 to March 2006 were reviewed retrospectively. Median age was 63 years (range, 16–81). The locations of the primary lesion were as follows: larynx in 18 patients, oropharynx in 11, nasopharynx in 7, hypopharynx in 7 and others in 4. Clinical stages were as follows: Stage II in 20 and Stages III–IV in 27. Almost all patients underwent platinum-based concomitant chemoradiotherapy. The median cumulative dose of cisplatin was 100 mg/m2 (range, 80–300) and median radiation dose was 70 Gy (range, 50–70).
Severe dysphagia (Grade 3–4) was observed in 22 patients (47%) as an acute toxic event. One patient required tube feeding even at 12-month follow-up. In univariate analysis, clinical stage (III–IV) (P = 0.017), primary site (oro-hypopharynx) (P = 0.041) and radiation portal size (>11 cm) (P < 0.001) were found to be associated with severe dysphagia. In multivariate analysis, only radiation portal size was found to have a significant relationship with severe dysphagia (P = 0.048).
Larger radiation portal field was associated with severe dysphagia induced by chemoradiotherapy.
Nuclear factor-B (NF-B) activation has been identified in a variety of solid tumors and lymphoid malignancies. The aim of our study was to determine the expression status and clinical significance of NF-B in extranodal natural killer (NK)/T-cell lymphoma, nasal type.
Tumor specimens from 23 patients with previously untreated NK/T-cell lymphoma initially treated with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) or CHOP-based chemotherapy were examined by immunohistochemistry for three NF-B subunits (p65, p50 and p52), which are involved in either the canonical or alternative pathway.
None of the cases could be detected with p65 or p50 nuclear staining. On the other hand, 15 (65.2%) cases had p52 nuclear staining, suggesting NF-B activation through the alternative pathway. All major clinical characteristics were balanced between NF-B p52-positive and -negative patients. The objective response rate achieved in NF-B-positive patients was significantly lower than that in negative patients (33.3% vs. 87.5%, P = 0.027). At a median follow-up of 25 months, 8 (53.3%) of 15 NF-B-positive patients had died compared with none of 8 NF-B-negative patients (P = 0.041). In a multivariate analysis, NF-B status and stage were identified to be independent prognostic factors.
Our results suggest that NF-B activation through the alternative pathway is frequently observed in NK/T-cell lymphoma and associated with chemoresistance and poor survival.
The aim of this study was to investigate the safety, pharmacokinetic and pharmacodynamic profiles of pegfilgrastim (KRN125), a long-acting granulocyte colony-stimulating factor, in lung cancer patients with chemotherapy-induced neutropenia.
Eighteen Japanese lung cancer patients who had experienced severe neutropenia (absolute neutrophil counts <0.5 x 109 cells/l) were enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose cohort (dose levels of 30, 60 or 100 µg/kg). Patients received the same chemotherapy regimen as in their previous cycle and pegfilgrastim was injected subcutaneously the day after chemotherapy ended in each treatment cycle. Pharmacokinetic, pharmacodynamic and safety analyses were performed.
Dose-limiting toxicity and serious adverse events related to pegfilgrastim were not observed in any patients. Pegfilgrastim antibodies were not detected. Maximum serum concentrations and area under the serum concentration–time curves of pegfilgrastim were dependent on the pegfilgrastim dose in a non-linear manner. Of the 18 patients, severe neutropenia occurred in 4 (22.2%), and, of these, 1 patient (5.5%) required rescue treatment by filgrastim.
A single dose of pegfilgrastim increases the serum concentration of pegfilgrastim for several days in a dose-dependent manner and is not associated with significant toxicity. Good efficacy of pegfilgrastim for the prevention of severe neutropenia was observed at all dose levels. Based on these data, further studies are warranted to determine the recommended dose of pegfilgrastim for Japanese patients with chemotherapy-induced neutropenia.
To find vertebral metastases with high risk of symptomatic malignant spinal cord compression (MSCC), features of vertebral metastases caused motor deficits of the lower extremities were examined.
From 2004 through 2006, 78 patients with metastases of the thoracic and/or the cervical spine were treated with radiation therapy (RT). Of these, 86 irradiated lesions in 73 patients were evaluable by magnetic resonance imaging and/or computed tomography at the initiation of RT and were reviewed retrospectively in this study. Twenty-eight patients (38%) had motor deficits at the initiation of RT. Assessed factors were age, sex, primary disease (lung, breast, digestive system and other cancer), lamina involvement, main level of tumor location and vertebral-body involvement.
Incidence of motor deficits at the initiation of RT was 55% for lesions with lamina involvement and 5% for lesions without lamina involvement (P < 0.0001). Incidence of motor deficits was 15% for lesions located mainly in the cervical spine and/or the upper thoracic spine (Th1–4), 54% for lesions located mainly in the middle thoracic spine (MTS) (Th5–8) and 30% for lesions located mainly in the lower thoracic spine (Th9–12) (P = 0.0095). Age, sex, primary disease and vertebral-body involvement were not statistically significant factors for incidence of motor deficits due to MSCC (P > 0.9999, P = 0.7798, P = 0.1702 and P = 0.366, respectively).
Vertebral metastases with lamina involvement tended to cause symptomatic MSCC. Latent development of MSCC occurred more frequently in the MTS compared with other levels of the thoracic and the cervical spine.
The National Polyp Study is used as the basis of recommendations for colonoscopic surveillance after polypectomy, establishing an interval of 3 years after removal of newly diagnosed adenomas. The aim of this retrospective cohort study was to estimate the incidence of advanced neoplasia after initial colonoscopy and compare the differences among risk groups.
Patients over 40 years who were referred for initial colonoscopy at six institutes were selected. They were classified into four groups based on the initial colonoscopy: A, patients without any adenoma; B, with adenomas of <6 mm only; C, with adenomas of ≥6 mm; D, with any intramucosal cancer. The index lesion (IL) at follow-up colonoscopy was defined as large adenoma ≥10 mm, intramucosal/invasive cancer.
A total of 5309 patients were enrolled in this study. Overall, median follow-up period was 5.1 years. The numbers of eligible patients in the various subgroups were A, 2006; B, 1655; C, 1123; D, 525. A total of 379 ILs were newly diagnosed during follow-up colonoscopy. The cumulative incidence of ILs in each group was A, 2.6%; B, 6.7%; C, 13.4%; and D, 12.6%.
Patients with any adenomas >6 mm or intramucosal cancer at the initial colonoscopy have a higher risk of advanced neoplasia during follow-up colonoscopy.
The aim of this study was to assess the non-inferiority of 1 mg to 3 mg granisetron (GRN) injection for the treatment of acute chemotherapy-induced nausea and vomiting (CINV) and to evaluate the tolerability of GRN given at 1 mg in Japanese cancer patients.
Patients with cancer receiving highly emetogenic chemotherapy were enrolled in this single-blind randomized controlled study. Patients were randomly assigned to receive GRN at a single dose of 1 or 3 mg. The primary endpoint was the rate of complete protection from emetic events (no vomiting, no retching and no need for rescue medication) during the first 24 h following the initiation of chemotherapy.
There were 89 patients in the 1 mg group and 90 patients in the 3 mg group. Complete protection was achieved in 70 patients (78.7%) in the 1 mg group and 73 (81.1%) patients in the 3 mg group. The one-sided test did not reveal non-inferiority of either dose of GRN to the other at a 5% significance level.
Our data failed to show the non-inferiority of 1 mg of GRN to 3 mg of GRN administered as a single dose. However, the rate of complete protection from nausea and vomiting was similar in the two groups. Given the recommended dosage in the guidelines and the economic need for reduction of medical care expenses in Japan, prophylactic administration of GRN at 1 mg may be an appropriate, alternative treatment for acute CINV in cancer patients.
Patients with multiple myeloma (MM) achieving high-quality responses, defined as a complete response (CR) and a very good partial response (VGPR) after transplant, benefit from high-dose therapy followed by autologous stem cell transplantation (ASCT). Induction pre-transplantation treatment with vincristine, doxorubicin and dexamethasone (VAD) is currently being replaced by new targeted agents with high anti-myeloma activity. The use of these novel agents may increase the CR + VGPR rate before ASCT, which may improve post-transplantation responses and survival.
We performed a retrospective analysis of 69 patients with MM who received bortezomib-containing regimens (n = 30) or VAD (n = 39) before collection of peripheral blood stem cells and ASCT.
Objective response rate (at least a partial response) prior to ASCT was documented in 27 (90%) of 30 and 31 (81.6%) of evaluable 38 patients with bortezomib-containing regimens and VAD, respectively. The difference between the two groups was not significant (P = 0.494). However, the high-quality response rate with VGPR or more in the bortezomib group was significantly higher compared with the VAD group (66.7% vs. 34.2%, respectively, P = 0.006). The superiority of bortezomib-containing regimens in the high-quality response rate remained significant for only the newly diagnosed patients (n = 16, P = 0.008). The engraftment data as well as stem cell harvesting were comparable between the two groups. The major bortezomib-related toxicities were thrombocytopenias and peripheral neuropathies; toxicities of VAD were hematologic and infectious. After ASCT, the difference between the two groups did not reach the level of statistical significance with respect to progression-free survival and overall survival (P = 0.498 and 0.835, respectively).
The results of this retrospective comparison of bortezomib-containing regimens with the VAD as induction treatment prior to ASCT for MM provided a demonstration of the superiority of bortezomib therapy in terms of achieving a high-quality response. However, survivals following ASCT did not differ according to the induction regimens.