Phase I Clinical Trial of Intravenous L-ascorbic Acid Following Salvage Chemotherapy for Relapsed B-cell non-Hodgkin's Lymphoma.

PURPOSE: To determine the safety and the appropriate dose of intravenous l-ascorbic acid (AA) in conjunction with chemotherapy for patients with relapsed lymphoma. PATIENTS AND METHODS: Patients with relapsed CD20-positive B-cell non-Hodgkin's lymphoma, who were going to receive the CHASER regimen as salvage therapy, were enrolled and treated with escalating doses of AA administered by drip infusion after the 2nd course of the CHASER regimen. The target plasma concentration immediately after AA administration was >15 mM (264 mg/dl). RESULTS: A serum AA concentration of >15 mM was achieved in 3 sequentially registered patients, all of whom had received a 75 g whole body dose. No obvious adverse drug reaction was observed in the patients. The trial was therefore successfully completed. CONCLUSION: Intravenous AA at a whole body dose of 75 g appears to be safe and sufficient to achieve an effective serum concentration. A phase II trial to evaluate the efficacy of intravenous AA in relapsed/refractory lymphoma patients will now be initiated.

Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy has become one of the standard management approaches for newly diagnosed localized nasal natural killer (NK)/T-cell lymphoma (NKTCL). Few data are available on the prognostic biomarkers of NKTCL among patients treated with concurrent chemoradiotherapy. To evaluate the prognostic significance of immunophenotypic biomarkers for patients treated with concurrent chemoradiotherapy, latent membrane protein 1 (LMP1), cutaneous lymphocyte antigen (CLA) and cell origin were examined in samples from 32 patients who were enrolled in the Japan Clinical Oncology Group 0211 trial and treated with concurrent chemoradiotherapy. LMP1 and CLA were positive in 66% (19/29) and 29% (9/31) of the cases examined, respectively. The median follow-up duration was 68 months (range, 61-94). The patients with LMP1-positive tumors showed a better overall survival (OS) than the patients with LMP1-negative tumors (hazard ratio, 0.240; 95% confidence interval [CI], 0.057-1.013; 80% CI, 0.093-0.615; P = 0.035). All five patients with LMP1-negative tumors who experienced disease progression died of lymphoma, and both patients with local failure had LMP1-negative tumors. There was no significant difference in OS according to CLA expression. A total of 27 (84%) cases were of NK-cell origin, two were of αß T-cell origin and three were of γδ T-cell origin. In contrast to those with tumors of NK-cell origin, all five patients with NKTCL of T-cell origin were alive without relapse at the last follow up. Our results indicate that LMP1 expression is a favorable prognostic marker and suggest that a T-cell origin of the tumor may be a favorable prognostic marker for patients with localized NKTCL treated with concurrent chemoradiotherapy.

Anemia affects the quality of life of Japanese cancer patients.

The Functional Assessment of Cancer Therapy-Anemia (FACT-An) was developed to measure the effect of anemia on quality of life (QOL) in cancer patients. We have previously validated the Japanese version of the FACT-An in Japanese cancer patients receiving chemotherapy, hormone therapy, or radiation therapy. That analysis was limited to evaluating the relationship between QOL scores and hemoglobin (Hb) levels. In this study, the data were further analyzed in order to identify factors that affect QOL. The mean Hb level of the patients was unchanged over three months. Patient age, Eastern Oncology Group Performance Status (ECOG-PS) score, Hb level, and the type of treatment method received were each predictive factors of a patient's FACT-An score at baseline, while the patient's Hb level at three months and whether the patient had received a blood transfusion were both predictive factors of a patient's FACT-An score at three months. Anemia consistently negatively affected the QOL of cancer patients measured over a three-month period. These results confirm the clinical effectiveness of the FACT-An as a tool to assess anemia-related QOL in Japanese cancer patients.

Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502.

A phase I/II trial of TS-1 combined with gemcitabine was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d. on days 1-14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In phase I (n=22), each cohort received escalating doses of TS-1 (30-40 mg/m(2) b.i.d.) and gemcitabine (800-1000 mg/m(2)); MTD was 40 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine; RD was 30 mg/m(2) b.i.d. TS-1 and 1000 mg/m(2) gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin toxicity, and stomatitis. In phase II (n=37), the overall response rate was 27% (90% confidence interval (CI): 15-42%) and the median time to progression and overall survival were 4.2 months (90% CI: 3.2-5.7) and 12.9 months (90% CI: 10.4-14.7), respectively. The most common grade 3 or higher toxicity was neutropenia (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each of grade 3 pneumonitis and skin toxicity were observed, but nonhematological toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a promising doublet regimen in elderly patients with advanced NSCLC with acceptable toxicities.

Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211.

PURPOSE: To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy. PATIENTS AND METHODS: Treatments comprised concurrent radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC). Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status (PS) of 0 to 2 were eligible for enrollment. The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose. RESULTS: Of the 33 patients enrolled, 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose. Twenty-seven patients (range, 21 to 68; median, 56 years) treated with the recommended dose showed the following clinical features: male:female, 17:10; stage IE, 18; stage IIE, 9; B symptoms present, 10; elevated serum lactate dehydrogenase, 5; and PS 2, 2. With a median follow-up of 32 months, the 2-year overall survival was 78% (95% CI, 57% to 89%). This compared favorably with the historical control of radiotherapy alone (45%). Of the 26 patients assessable for a response, 20 (77%) achieved a complete response, with one partial response. The overall response rate was 81%. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed. CONCLUSION: Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.

Clinical validity of the Japanese version of the Functional Assessment of Cancer Therapy-Anemia Scale.

GOALS OF WORK: The purpose of this study was to reveal the clinical validity of the Japanese version of the Functional Assessment of Cancer Therapy-Anemia scale (FACT-An) in relation to hemoglobin level. We also analyzed patients' scores for the related FACT-General scale (FACT-G), the FACT Anemia subscale, and the FACT Trial Outcome Index-Anemia scale (FACT TOI-An) to determine which was the most sensitive to anemia measurements. MATERIALS AND METHODS: Throughout Japan, we recruited 227 patients (mean+/-SD, 59+/-12.1 years old) diagnosed with a variety of cancers. We correlated the severity of anemia, as measured by hemoglobin levels, to scores on the FACT-An and on the other scales at baseline and at 3 months. MAIN RESULTS: The questionnaire completion rate was more than 98% at both time points. The FACT-An had high internal consistency (Cronbach's alpha coefficient >0.8). FACT-An scores were significantly and positively correlated with hemoglobin levels both at baseline (r=0.24; 95% CI=0.12 to 0.36; n=225) and at 3 months (r=0.24; 95% CI=0.10 to 0.36; n=204). FACT-G, FACT Anemia subscale, and FACT TOI-An scores also successfully discriminated between patients with lower (Hb <11.0 g/dl) and higher (Hb > or =11.0 g/dl) hemoglobin levels. Moreover, the changes of these FACT scores over 3-months could discriminate changes in hemoglobin level. CONCLUSION: The Japanese version of the FACT-An has higher clinical validity and can be used to appropriately assess health-related quality of life among Japanese cancer patients with anemia.

Health-related quality of life among Japanese women with iron-deficiency anemia.

Iron-deficiency anemia (IDA) is a common disease in females of childbearing age. Although iron supplementation quickly improves laboratory-measured parameters, its effect on health-related quality of life is unknown. Here, we conducted a prospective follow-up study to evaluate health-related quality of life in pre-menopausal women diagnosed with IDA. A convenience sample of 92 patients who visited Tokai University Hospital and three other affiliated hospitals were asked to fill out the Medical Outcome Study 36-item short-form health survey (SF-36) during the course of treatment (baseline, and 1 and 3 months after the start of treatment). At baseline, vitality and general health scores were significantly lower than the Japanese national norms. After the start of therapy, however, a significant improvement was seen in all domain scores except role emotional (RE), and at 3 months all eight scores were comparable to or greater than the national norms. In particular, physical functioning and vitality scores of patients with a lower hemoglobin level ( < 9.0 g/dl) at baseline showed a dramatic improvement. Iron supplementation in IDA patients improves not only hemoglobin levels, but also physical function, vitality, and general health perception.