Treatment preferences among Japanese patients and physicians for epidermal growth factor receptor-mutant non-small cell lung cancer.

INTRODUCTION: Evidence is limited on preferences of Japanese patients and physicians in treatment for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Several oral or intravenous novel agents for EGFR exon 20 insertions are under development. The aim of our study was to investigate which attributes of novel treatments influenced selection of oral or intravenous agents among treated patients and treating physicians in Japan. METHODS: The study was designed by board-certified oncologists, patient representatives, and analytics specialists. Eligible participants completed an online survey with a discrete choice experiment presenting two treatment profiles described by attributes: mode of administration (oral or intravenous); frequency of administration; overall response rate (ORR); average progression-free survival (PFS); chance of experiencing severe side effects (SEs); mild-moderate gastrointestinal SEs; mild-moderate skin-related SEs; and patient out-of-pocket costs. RESULTS: Fifty-four patients (all self-reported EGFR-mutant) and 74 physicians participated from December 2021 to August 2022. All attributes being equal, there was greater preference for oral administration. However, there was greater preference for intravenous over oral, when ORR and PFS improved by 10% and 1 month, and severe SEs reduced by 10%. Physicians exhibited greater preference for PFS compared to patients (p < 0.01). Ranked order of attribute importance was as follows: (1) PFS; (2) ORR; (3) severe SEs, expressed by patients and physicians alike. CONCLUSIONS: Our study revealed Japanese physician and patient preferences in treatment options for EGFR-mutant NSCLC. Compared to the strong preference for a more efficacious drug, the preference of oral versus intravenous revealed a smaller impact.

A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy.

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan. METHODS: We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. The primary end point was response rate (assessed by a central imaging reviewer). RESULTS: From August 2020 to February 2021, 55 patients from 15 institutions were enrolled in the study. The overall response for primary analysis was achieved in 16 patients (29.1 %; 95 % CI, 17.6-42.9), which exceeded the threshold response rate necessary for analysis. Stable disease was found in 16 patients (29.1 %), and progressive disease, in 18 (32.7 %). The median length of progression-free survival (PFS) was 4.07 months (95 % CI 2.10-4.30), and the rate of 12-month PFS was 17.3 %. CONCLUSIONS: Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.

Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations.

Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients' reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients.

Assessing the quality of cancer screening leaflets using the International Patient Decision Aids Standards instrument: A cross-sectional content analysis.

OBJECTIVE: To assess the quality of national cancer screening program leaflets in Japan from the informed-decision perspective. METHODS: Cross-sectional content analysis of invitation leaflets issued by centralized organizations and used nationwide in Japan was conducted. Three members independently evaluated the materials using International Patient Decision Aids Standards six-item minimum criteria for qualifying patient decision aids. PATIENT PUBLIC INVOLVEMENT: Co-author KH is a cancer patient himself. We also sought feedbacks from three other cancer survivors and two bereaved family members. RESULTS: Inter-rater agreement was substantial (Fleiss' kappa=0.62). The median score was 2 out of 6 (range: 2-3). All leaflets described the cancer (Q1: 7/7) and screening modality (Q2: 7/7). None stated not undergoing screening as an option. One stated another screening modality (Q3: 1/7). None stated both the positive and negative features of multiple options (Q4: 0/7. Q5: 0/7). One described the psychological and social experience of screening but only its positive side (Q6: 1/7). CONCLUSIONS: There is room for improvement in the content of the public cancer screening invitation leaflets in Japan from informed-decision perspective. PRACTICE IMPLICATIONS: Cancer screening leaflets should provide evidence-based, well-balanced, easy-to-understand information to educate people on cancer screening while maintaining people's autonomy.

A Phase II Study to Assess the Efficacy of Osimertinib in Patients With EGFR Mutation-positive NSCLC Who Developed Isolated CNS Progression (T790M-negative or Unknown) During First- or Second-generation EGFR-TKI or Systemic Disease Progression (T790M-negative) After Treatment With First- or Second-generation EGFR-TKI and Platinum-based Chemotherapy (WJOG12819L).

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has recently been established as a standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC). However, only about one-half of patients who have received prior treatment with a first- or second-generation EGFR-TKI are eligible for osimertinib therapy because its indication in the second-line setting is limited to metastatic NSCLC positive for the T790M resistance mutation of EGFR. The dose-escalation part of a study in which patients received osimertinib at doses of 20 to 240 mg once daily after the development of resistance to first- or second-generation EGFR-TKIs revealed a response rate of 21% and a median progression-free survival of 2.8 months for individuals whose tumors were negative for EGFR T790M. We have now designed a phase II study of osimertinib for patients with EGFR mutation-positive NSCLC who develop isolated central nervous system progression (T790M-negative or unknown) after first- or second-generation EGFR-TKI therapy (cohort 1) or who develop systemic disease progression (T790M-negative) after first- or second-generation EGFR-TKI therapy and platinum-based chemotherapy (cohort 2). A total of 70 patients (cohort 1, n = 17; cohort 2, n = 53) will be enrolled in this study, which originated from a suggestion of a dedicated network for patients with lung cancer in Japan.

Importance of doctor-initiated management of the balance between work and treatment for lung cancer patients: Results of a nationwide survey by the Japan Lung Cancer Society.

BACKGROUNDS: Since the recent development of molecular targeted drugs and immune checkpoint inhibitors has improved lung cancer treatment options and outcomes, supporting patients in balancing work and pharmacotherapy have become even more important in the field of lung cancer treatment. This study sought to identify the current status and roles of doctors in balancing work and treatment for lung cancer patients. METHODS: Patients and doctors were recruited to complete a web-based questionnaire survey by the Japan Lung Cancer Society. RESULTS: About 287 lung cancer patients and 381 doctors were included in the analysis. About 42.9% of patients responded that "there was no discussion" about their working conditions or work before the initiation of pharmacotherapy, while 22.6% responded that "there was an inquiry from a doctor/health care provider and a discussion that included the doctor was held." About 45.3% of patients took leave or resigned from work at the time of diagnosis. The most common reasons for patients to resign before or during pharmacotherapy were "poor physical condition due to side effects of treatment or illness" and "concern about causing problems in the workplace." To assist in balancing work and pharmacotherapy, patients desired "increased opportunities to consult about work" (36.9%) and "provision of treatment options with few adverse events" (28.9%). CONCLUSION: This study highlights the importance of doctor-initiated management of the balance between work and treatment for lung cancer patients. An important first step is for doctors themselves to take an interest in their patients' professions and initiate discussions of work-related topics with their patients.

The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV.

According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.

Fabrication of a laser cavity mirror in a large mode area fiber by an ultrashort pulse laser.

We present herein a method to fabricate a higher-order fiber grating (HOFG) for use as a fiber-cavity mirror in a fiber laser. The HOFG was fabricated by irradiating the Yb-doped large core of a double-clad fiber by a femtosecond pulsed laser. The HOFG served as a laser cavity mirror with a reflectance of 13.2% and yielded a laser line with a spectral full width at half-maximum of 0.56 nm.

Fabrication of long-period fiber gratings using end-coupled ultrafast laser pulses.

We propose a novel technique for the fabrication of long-period fiber gratings (LPFGs) using ultrafast laser pulses coupled into opposite ends of an optical fiber. The pulses counter-propagate in the fiber and induce a permanent refractive index change where they overlap. Based on absorption rate measurements, it was confirmed that the pulses were partially absorbed at the overlapping position, with a maximum absorption rate of 6%. Furthermore, a LPFG with a smooth transmission spectrum and low background loss was successfully fabricated using this technique.

Energy transfer efficiency from Cr(3+) to Nd(3+) in solar-pumped laser using transparent Nd/Cr:Y(3)Al(5)O(12) ceramics.

We report energy transfer efficiency from Cr3+ to Nd3+ in Nd (1.0 at.%)/Cr (0.4 at.%) co-doped Y3Al5O12 (YAG) transparent ceramics in the laser oscillation states. The laser oscillation has performed using two pumping lasers operating at 808 nm and 561 nm; the former pumps Nd3+ directly to create the 1064 nm laser oscillation, whereas the latter assists the performance via Cr3+ absorption and sequential energy transfer to Nd3+. From the laser output power properties and laser mode analysis, the energy transfer efficiency was determined to be around 65%, which is close to that obtained from the spontaneous Nd3+ emission.

Atherogenic phenotype remains in elderly diabetic patients.

AIM: It is known that plasma low-density lipoprotein cholesterol (LDL-C) levels tend to decrease with age. Thus, most elderly diabetic patients often show normal LDL-C levels. Therefore, the present study was carried out to examine whether elderly diabetic patients show "the atherogenic phenotype" even if their LDL-C is not elevated. METHODS: The study participants consisted of 236 patients. They were separated into four groups according to their age (below 64 years and above 65 years) and an association of type 2 diabetes. A total of 88 middle-aged diabetic, 34 middle-aged non-diabetic, 64 elderly diabetic and 50 elderly non-diabetic participants were enrolled. LDL-C, small dense LDL-C (sLDL-C) were investigated. ANOVA were used for comparison of LDL-C, sLDL-C and the sLDL-C/LDL-C ratio between the four groups. Multivariate regression analysis was carried out in order to find the independent factors associated with the sLDL-C/LDL-C ratio. RESULTS: Among the four groups, the LDL-C of the elderly diabetic group showed lower LDL-C levels compared with that of middle-aged diabetic group, although the difference was not significant (128.6 ± 38.7 vs 138.4 ± 35.8 mg/dL). In contrast, sLDL-C and the sLDL-C/LDL-C ratio in the elderly diabetic group were both higher than those of the elderly non-diabetic group (47.0 ± 24.2 mg/dL and 0.36 ± 0.14 mg/dL, vs 21.4 ± 16.7 mg/dL and 0.19 ± 0.11 mg/dL, P < 0.05). Multivariate regression analysis showed that age, sex, the presence of diabetes mellitus and plasma triglyceride were the independent factors determining the sLDL-C/LDL-C ratio. DISCUSSION: It is concluded from the present data that the atherogenic phenotype remains in elderly diabetic patients even if their LDL-C is not elevated.

Febuxostat (Feburic tablet) in the management of hyperuricemia in a general practice cohort of Japanese patients with a high prevalence of cardiovascular problems.

Hyperuricemia is increasing in prevalence and this is paralleled by an increased incidence of acute gout. In addition, there is growing evidence of an association between high serum levels of uric acid (sUA) and cardiovascular disease (CVD). In this preliminary report, we present 12-16 week results from a multicenter, general practice study in which we evaluated the usefulness of febuxostat in a cohort of untreated patients with hyperuricemia with a high prevalence of CVD. Febuxostat titrated from 10 mg/day up to 40 mg/day resulted in statistically significant and clinically relevant reductions in sUA after 12-16 weeks. A "responder" level of 6.0 mg/dL or lower was achieved in 95 of 100 (95%) patients. Significant reductions in sUA were achieved regardless of the presence/absence of coexisting diseases (e.g. CVD, renal insufficiency, diabetes and obesity) or the class of antihypertensive agent being used by the patient. No serious adverse reactions were noted with febuxostat. Although allopurinol has been used generally for hyperuricemia/gout, it is excreted fully via the kidneys, restricting its use in patients with reduced renal function, and its three-times-daily administration leads to poor adherence. Based on the results of this study, febuxostat may provide an easier option than allopurinol for clinicians specializing in CVDs.

Laser emission from a solar-pumped fiber.

We report the realization of a solar-pumped fiber laser (SPFL) using a double-clad (a center core/ an inner clad working also as optical waveguide/ an outer clad) Nd-doped fluoride optical fiber as a laser medium. With a compact off-axis parabolic mirror of 5 cm in aperture diameter, the natural sunlight is concentrated by a factor 104, and introduced partly into the core of the fiber and partly into the inner clad in which the light is guided in some distance and transferred to the core after all. We have obtained clear laser spectrum characteristics with approximately 0.01 nm full-width-half-maximum of the laser line at the peak wavelength of 1053.7 nm, a low-lasing threshold of 49.1 mW, a slope efficiency of 6.6%, and a total efficiency of 1.76%. Further optimization of the medium properties, optical cavity, and concentration technique will yield higher efficiency and lower threshold.

Causes of decreased activity of daily life in elderly patients who need daily living care.

AIM: The causes of decreased activity of daily life (ADL) in elderly patients include cerebrovascular diseases, bone fracture by falls, and dementia. The present study was conducted among elderly patients with decreased ADL who were hospitalized in nursing wards in order to investigate the causes of becoming early bedridden and to determine precautionary measures against decreased ADL. METHODS: The study subjects were 224 elderly patients with decreased ADL (mean age: 83.3 ± 8.0 years) and 49 outpatients without decreased ADL (mean age: 76.8 ± 5.3 years). Current age, age at the start of ADL decrease, medical history and history of smoking were investigated. RESULTS: In the groups with decreased ADL, current age and the age of becoming bedridden in non-diabetic versus diabetic groups were 84.7 ± 7.9 versus 80.3 ± 7.5 and 82.7 ± 8.3 versus 77.6 ± 8.0 years, respectively, both showing significantly lower values in the diabetic group (P < 0.05). Multiple regression analysis revealed that sex difference and diabetes were the factors determining the age of becoming early bedridden. Diabetic patients with smoking habit were significantly younger than diabetic and non-diabetic patients without smoking habit. CONCLUSION: Sex difference, smoking habit and presence of diabetes mellitus are independent risk factors of becoming early bedridden. Therefore, the major targets of medical care among elderly should be diabetic men with a smoking habit to lower the risks of decreased ADL.

The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia.

AIM: To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption, we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis, lipid and glucose metabolism, and markers of obesity and inflammation. METHODS: A total of 120 patients with dyslipidemia (46 men; mean age 66.5 years), who had not achieved the low density lipoprotein cholesterol (LDL-C) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy, were enrolled and additionally treated with ezetimibe (10 mg/day) for 12 weeks. RESULTS: Compared to the baseline, LDL-C was reduced by 19.2% (p<0.001) after ezetimibe monotherapy and by 24.7% (p<0.001) after co-administration with ezetimibe and any statin. Ezetimibe therapy decreased cholesterol absorption markers and increased a cholesterol synthesis marker. Treatment with ezetimibe reduced the fasting serum insulin level (p<0.05) and HbA1c (p<0.05), increased serum adiponectin (p<0.01), and showed a significant decrease of high-sensitive C-reactive protein (hsCRP, p<0.01). No adverse events occurred during the study. CONCLUSION: Thus, cholesterol absorption inhibition by ezetimibe is an important therapeutic strategy since LDL-C and cholesterol absorption markers had a positive correlation. Ezetimibe not only reduced the serum LDL-C level but also improved glucose metabolism as well as obesity and inflammation markers. These findings support the benefit of ezetimibe as a new option for the treatment of dyslipidemia.

Phase I study of combination chemotherapy with irinotecan hydrochloride and nedaplatin for cervical squamous cell carcinoma: Japanese gynecologic oncology group study.

The aim of this study (JGOG1063) was to determine the recommended dose (RD) for combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin (NDP) for advanced cervical squamous cell carcinoma. CPT-11 was given intravenously in fixed doses of 60 mg/m2 on days 1 and 8 and NDP, in escalating doses, on day 1, every 4 weeks. A total of 15 patients were enrolled in the study. At level 1 (NDP: 50 mg/m2), one of the 3 patients developed grade 3 diarrhea, so 3 additional patients were enrolled at this level. As none of the 3 additional patients exhibited dose-limiting toxicity, level 1 was elevated to level 2 (NDP: 60 mg/m2). The maximum tolerated dose was not reached, even at the highest dose level (level 4; NDP: 80 mg/m2). No further dose escalation was carried out, and level 4 (CPT-11: 60 mg/m2, NDP: 80 mg/m2) was determined as the RD.

Phase I study of irinotecan combined with mitomycin-C and 5-fluorouracil for gynecological malignancies: the JGOG study.

BACKGROUND: A phase I study to evaluate combined therapy with irinotecan (CPT-11), mitomycin-C (MMC), and 5-fluorouracil (5-FU) was performed in patients with gynecological malignancy, especially non-squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Eligibility for the study included patients with previously untreated, chemotherapy-naïve cervical and ovarian carcinoma. CPT-11 and MMC were administered on days 1 and 15 by intravenous infusion, while 5-FU was given on days 3 to 7. This regimen was repeated after 5 weeks. Four escalating dose levels were carried out (CPT-11/MMC: 120/5, 120/6, 150/6, and 150/7 mg/m2; 5-FU 600 mg/m2 fixed). RESULTS: Fourteen patients were enrolled in the study. Although all the patients had no previous chemotherapy, three patients had undergone a simple hysterectomy and nine had a radical hysterectomy performed before this chemotherapy. The maximum tolerated dose was not reached by using CPT-11 150 mg/m2, MMC 7 mg/m2, and 5-FU 600 mg/m2 because none of the patients experienced any hematological or non-hematological toxicities of grade 4 during the first cycle. CONCLUSION: The recommended doses of this new regimen are CPT-11 150 mg/m2, MMC 7 mg/m2, and 5-Fu 600 mg/m2 which can be well tolerated for gynecological malignancies.

Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.

BACKGROUND: To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer. METHODS: Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy. RESULTS: The 5-year survival of patients with high-dose and low-dose Z-100 was 41.5% (95% CI: 31.7-51.3%) and 58.2% (95% CI: 48.7-67.7%), respectively, showing a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458-0.980], P = 0.039). Survival of high-dose group was equivalent to the 4-year survival of the radiotherapy plus hydroxyurea arm (49.7%) of GOG120 study, and that of low-dose group was similar to the survival of the cisplatin-based chemoradiation arm. The progression-free survival was also significantly improved in favor of low-dose group (hazard ratio: 0.667 [95% CI: 0.447-0.997], P = 0.048). The survival of low-dose group was similar to the survival of the cisplatin-based chemoradiation arms of the GOG120 study. CONCLUSIONS: Unexpectedly, the survival of patients with advanced cervical cancer treated by lower dose of Z-100 in combination with radiotherapy was significantly better than those treated with higher dose Z-100, which was equivalent to the survival with radiotherapy alone. The hypothesis that lower dose of Z-100 enhances the efficacy of radiation therapy is now being tested by placebo-controlled randomized trial.

Global prevalence of dementia: a Delphi consensus study.

BACKGROUND: 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. METHODS: 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. FINDINGS: Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24.3 million people have dementia today, with 4.6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81.1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. INTERPRETATION: We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.

[A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer].

Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m2 as Level 1 or at 90 mg/m2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6.patients receiving 80 mg/m2 of CDGP and in all 2 patients receiving 90 mg/m2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was PR or better in all patients. The CR rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration of CDGP at 80 mg/m2 on Days 1 and 29 is safe and effective.