Phase II study of S-1 plus docetaxel as first-line treatment for older patients with advanced gastric cancer (OGSG 0902).

BACKGROUND: Although there is insufficient evidence for the treatment of older patients with advanced gastric cancer, fluorouracil combined with platinum chemotherapy has been recognized as a standard first-line treatment for such populations in Japan despite the lack of efficacy and toxicity data. METHODS: Patients aged 75 years or older with advanced gastric cancer were enrolled. S-1 plus docetaxel (docetaxel: 40 mg/m2, day 1; S-1: 80 mg/m2, days 1-14; q21 days) was repeated every 3 weeks. The primary endpoint was overall response rate. Secondary endpoints were safety, progression-free survival, time to treatment failure, and overall survival. The sample size was calculated as 30 under the hypothesis of an expected response rate of 40% and a threshold response rate of 20%, at a power of 90% and a two-sided alpha value of 5%. RESULTS: From February 2010 to January 2015, 31 patients were enrolled and assessed for efficacy and toxicity. The response rate was 45.2% (95% CI 27.3%-64.0%; p = 0.001) and it exceeded the expected response rate set at 40%. Median progression-free survival was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1 months. The major grade 3/4 adverse events were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). CONCLUSIONS: These findings indicate that S-1 plus docetaxel as first-line treatment for older patients is feasible and that it has promising efficacy against advanced gastric cancer.

The Phase II Study of Panitumumab in Chemotherapy-Naïve Frail or Elderly Patients with RAS Wild-type Colorectal Cancer: OGSG 1602 Final Results.

BACKGROUND: We previously reported the response rate of a phase II OGSG1602 study on panitumumab in chemotherapy-naive frail or elderly patients with RAS wild-type unresectable colorectal cancer (CRC) [Terazawa T, Kato T, Goto M, et al. Oncologist. 2021;26(1):17]. Herein, we report a survival analysis. METHODS: Patients aged ≥65 years and considered unsuitable for intensive chemotherapy or aged ≥76 years were enrolled. Primary tumors located from the cecum to the transverse colon were considered right-sided tumors (RSTs); those located from the splenic flexure to the rectum were considered left-sided tumors (LSTs). RESULTS: Among the 36 enrolled patients, 34 were included in the efficacy analysis, with 26 and 8 having LSTs and RSTs, respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.0 [95% CI, 5.4-10.0] and 17.5 months (95% CI, 13.8-24.3), respectively. Although no significant differences existed in PFS between patients with LST and RST {6.6 (95% CI, 5.4-11.5) vs. 4.9 months [95% CI, 1.9-not available (NA), P = .120]}, there were significant differences in OS [19.3 (95% CI, 14.2-NA) vs.12.3 months (95% CI, 9.9-NA), P = .043]. CONCLUSION: Panitumumab showed favorable OS in frail or elderly patients with RAS wild-type CRC and no prior exposure to chemotherapy. Panitumumab may be optimal for patients with LSTs (UMIN Clinical Trials Registry Number UMIN000024528).

Phase II Study of Panitumumab Monotherapy in Chemotherapy-Naïve Frail or Elderly Patients with Unresectable RAS Wild-Type Colorectal Cancer: OGSG 1602.

LESSONS LEARNED: Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild-type unresectable colorectal cancer. It is especially effective for left-sided tumors; therefore, panitumumab as first-line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin-based or irinotecan-based combination regimens. BACKGROUND: First-line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy-naïve frail or elderly patients with unresectable RAS wild-type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first-line treatment. METHODS: We conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities. RESULTS: Thirty-six patients (median age: 81 [range, 67-88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty-three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty-eight patients (77.8%) had left-sided CRC, whereas eight (22.2%) had right-sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4-67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5-87.7). The RR of patients with left- and right-sided tumors was 65.4% (95% CI, 44.3-82.8) and 0.0% (95% CI, 0.0-36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%). CONCLUSION: Panitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.

Efficacy of the eribulin, pertuzumab, and trastuzumab combination therapy for human epidermal growth factor receptor 2-positive advanced or metastatic breast cancer: a multicenter, single arm, phase II study (JBCRG-M03 study).

Purpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013-April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0-11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.

[A Case of Thymic Carcinoma of Postoperative Liver and Mediastinal Lymph Node Metastases Where Long-Term Survival Was Achieved through Multidisciplinary Treatment].

The patient was a 67-year-old man. At the age of 60, he underwent resection of thymic carcinoma with partial resection of the right upper lobe of the lung because of invasive thymic carcinoma. The pathological diagnosis was Masaoka stage Ⅲ squamous cell carcinoma. Follow-up examination 2 years after surgery showed metastases to the mediastinall ymph node and liver. After undergoing radiotherapy of 50 Gy to the mediastinal lymph node metastasis, partial hepatectomy was performed for metastatic liver cancer. Post-operation, he received 4 courses of combination therapy of carboplatin and paclitaxel. Five years post-hepatectomy, the patient developed liver metastasis again and underwent hepatectomy for local control. Postoperative recurrent cases of thymic carcinoma generally have poor prognosis. We describe a patient with thymic carcinoma of postoperative liver and mediastinal lymph node metastases who achieved long-term survival through multidisciplinary treatment.

First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients with advanced gastric cancer: a multicenter propensity score matched study.

BACKGROUND: Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. METHODS: In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. RESULTS: PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p < 0.001 each). CONCLUSION: Our findings do not support the survival benefit of SP over S-1 in elderly patients with AGC. We are now conducting a prospective comparative study to optimize treatment strategy and explore applicability of the geriatric assessment for these patients.

The distress and benefit to bereaved family members of participating in a post-bereavement survey.

BACKGROUND: Few studies have simultaneously collected quantitative data regarding the positive and negative effects of participating in post-bereavement surveys. METHODS: We conducted a cross-sectional postal questionnaire survey in October 2013. Potential participants were caregivers for family members who had died in four inpatient palliative care units, two home hospices, and a general hospital. We collected opinions regarding the distress and benefit of completing a post-bereavement survey. After collecting data, we provided feedback to participating institutions in the form of study results and de-identified open-ended comments. RESULTS: Of 692 potential participants, 596 were sent questionnaires; 393 returned questionnaires were valid and analyzed. Of the respondents, 62% reported being distressed by completing the questionnaire. Female participants and those who were mentally ill during the caregiving period reported more distress. However, 86% of respondents reported they found the questionnaire beneficial. Better quality of end-of-life care and respondent depression were associated with more benefit. Major benefits were: contributing to the development of end-of-life care as a family (63%); expressing gratitude to the hospital and medical staff (60%); and looking back and reflecting on the end-of-life period (40%). Feeling benefit was not correlated with feeling distressed (P = -0.02). CONCLUSION: In this large-scale study on the effects of post-bereavement surveys in Japan, many bereaved family members reported that completing the survey was beneficial. In addition to possibly having feelings of distress, post-bereavement surveys might also be beneficial to end-of-life care facilities.

Development the Care Evaluation Scale Version 2.0: a modified version of a measure for bereaved family members to evaluate the structure and process of palliative care for cancer patient.

BACKGROUND: The Care Evaluation Scale (CES1.0) was designed to allow bereaved family members to evaluate the structure and process of care, but has been associated with a high frequency of misresponses. The objective of this study was to develop a modified version of CES1.0 (CES2.0) that would eliminate misresponses while maintaining good reliability and validity. METHODS: We conducted a cross-sectional questionnaire survey by mail in October 2013. The participants were bereaved family members of patients who died from cancer in seven institutions in Japan. All family members were asked to complete CES2.0, the short form CES1.0, items on overall care satisfaction, the Family Satisfaction with Advanced Cancer Care (FAMCARE) Scale, the Patient Health Questionnaire-9 (PHQ-9) and the Brief Grief Questionnaire (BGQ). To examine test-retest reliability, all participants were asked to complete a second CES2.0. RESULTS: Of 596 questionnaires sent, 461 (77%) were returned and 393 (66%) were analyzed. In the short form CES1.0, 17.1% of the responses were identified as misresponses. No misresponses were found in CES2.0. We identified 10 CES2.0 subscales similar to those in CES1.0 using exploratory factor analysis. Cronbach's alpha was 0.96, and the intraclass correlation coefficient was 0.83. Correlations were found between CES2.0 and overall satisfaction (r = 0.83) and FAMCARE (r = 0.58). In addition, total CES2.0 scores were negatively correlated with the PHQ-9 (r = -0.22) and BGQ (r = -0.10). CONCLUSION: These results suggest that CES2.0 eliminated misresponses associated with CES1.0 while maintaining good reliability and validity and greatly improving test-retest reliability.

[A Case of Triple Negative Spindle Cell Carcinoma of the Breast and Improved Quality of Life Following Irinotecan Chemotherapy].

We report a case of triple negative spindle cell carcinoma of the breast, responsive to irinotecan chemotherapy. A 49-year old woman who had a tumor in the chest wall with a skin ulcer visited our hospital. After being diagnosed with triple negative spindle cell carcinoma of the breast, she underwent surgery, adjuvant chemotherapy, and radiation at the other hospital. Fourteen months after the surgery, she developed an ipsilateral breast tumor as a result of local recurrence. Since eribulin and paclitaxel plus bevacizumab chemotherapies were not effective, she was transferred to our hospital, and we administered irinotecan as third-line chemotherapy. Skin lesions and effusion were reduced and her quality of life improved for 4 months.

[A Case of Unresectable Locally Advanced Pancreatic Cancer Resulted in R0 Surgery after Chemotherapy].

A 67-year-old man visited our hospital for jaundice. Abdominal dynamic CT showed the hypovascular tumor at the head of the pancreas that surrounded superior mesenteric artery(SMA)at an angle of 220 degree. No metastasis in lymph nodes and other organs was observed. We diagnosed the tumor unresectable locally advanced(UR-LA)pancreatic cancer. Chemotherapy was administered with gemcitabine and nab-paclitaxel(GEM+nab-PTX)and achieved partial response. Regression in size and in range around SMA to an angle of 150 was observed. We assessed it possible to resect the tumor curatively, and performed subtotal stomach preserving pancreaticoduodenectomy and dissection of the plexus around the SMA, resulted in R0 surgery. Adjuvant chemotherapy was administered, and no recurrence was observed up to present, more than a year. It is suggested that GEM+nab-PTX can be effective as the primary therapy against UR-LA pancreatic cancer.

Measuring motivation for medical treatment: confirming the factor structure of the Achievement Motivation Index for Medical Treatment (AMI-MeT).

BACKGROUND: Developments in chemotherapy have led to changes in cancer care in Japan, with the government promoting a transition to outpatient chemotherapy. This requires patients and their families to participate more actively in treatment than in the past. However, it remains unclear how patients' motivation for medical treatment affects clinical consultations with their physicians. To investigate this, we developed a psychological index called the Achievement Motive Index for Medical Treatment (AMI-MeT), which comprises self-derived achievement motivation (AMS) and achievement motivation derived from others (AMO). However, its factor structure has not yet been confirmed in populations other than healthy university students. Thus, the aims of this study were to confirm the factor structure of the AMI-MeT in other groups and to determine the convergent and divergent validity of the AMI-MeT. METHODS: The AMI-MeT was administered to university students (n = 414), apparently healthy workers (n = 154), and cancer patients (n = 51). Multi-group confirmatory factor analysis was conducted and the mean scores of the AMI-MeT were compared between the groups. Correlations between the AMI-MeT and the Self-Construal Scale, comprising independent self-construal (IndSC) and interdependent self-construal (InterSC) subscales, were investigated in another group of students (n = 335). RESULTS: The multi-group confirmatory factor analysis supported a two-factor structure of the AMI-MeT: the weak invariance model was the best fit for the data. The mean scores of the AMI-MeT in apparently healthy workers and cancer patients were significantly higher than that in students (P < .01). The correlation analysis revealed that AMS scores were associated with IndSC scores (r = .25, P < .01) and AMO scores with InterSC scores (r = .30, P < .01). CONCLUSION: The two-factor model of the AMI-MeT was deemed appropriate for all three groups, and the subscales of the AMI-MeT successfully reflected the self and other dimensions. The AMI-MeT appears to be an effective tool for measuring medical treatment motivation, making it useful in participant observational research on medical consultations for Japanese cancer treatment.

[Predicting the Prognosis of Terminal Cancer Patients with Chemotherapy].

To determine the chemotherapy indication of terminal cancer patients, predicting the prognosis is meaningful. We intended to establish a suitable prognosis prediction index for these patients. From June 2015 to January 2016, we examined the prognosis in 7 patients who were administered chemotherapy drugs within 4 weeks before or after the prognosis calculation. Palliative prognostic index(PPI)was calculated prospectively, and prognosis in palliative care study(PiPS)was calculated prospectively or retrospectively. If patients had laboratory data within 4 days before prognosis calculation, they were assessed with PiPS-B. If patients did not have recent data, they were assessed with PiPS-A. The absolute agreement of prognosis index with actual survival was 100% in PPI, and 40.0% in PiPS. All patients who were administered chemotherapy after the PPI calculation were considered to have survived for more than 42 days. We concluded that PPI was a suitable prognosis prediction index for terminal cancer patients with chemotherapy. PPI was useful for determining the chemotherapy indication in these patients.

Use of glucose solution for the alleviation of gemcitabine-induced vascular pain: a double-blind randomized crossover study.

PURPOSE: Gemcitabine is widely used for chemotherapy in many types of cancers. However, vascular pain frequently occurs during its infusion, which can be serious enough to cause treatment discontinuation. This study was conducted to determine whether dissolution with 5 % glucose solution would relieve vascular pain compared with the approved use of saline as the diluent. METHODS: Patients with cancer who were treated with weekly gemcitabine were eligible. Vascular pain was assessed during two consecutive administrations in a double-blind, randomized crossover study. One group was scheduled to receive gemcitabine dissolved in saline followed by gemcitabine in 5 % glucose solution. In the other group, 5 % glucose solution was followed by saline. The primary endpoint was frequency of vascular pain for the total infusions of each solvent and the secondary endpoints were intensity, as assessed on a visual analogue scale and duration of vascular pain. RESULTS: Eighty-seven patients were randomly assigned to each treatment schedule. Frequency of vascular pain was significantly lower with 5 % glucose solution compared with saline (40 versus 63 %; p < 0.001). The intensity of vascular pain was also reduced with 5 % glucose solution compared with saline (mean, 1.3 versus 2.7 points; p < 0.001). There was no significant statistical difference in duration of vascular pain between the 5 % glucose solution and saline solution groups (mean, 21 versus 18 min; p = 0.420). CONCLUSIONS: The use of 5 % glucose solution to dissolve gemcitabine significantly reduced the frequency and the intensity of vascular pain compared with the use of saline.

Difference in survival and prognostic factors between smokers and never-smokers with advanced non-small-cell lung cancer.

BACKGROUND: Our aims were to investigate whether the association between smoking and survival is significant when adjusted for prognostic factors including use of epidermal growth factor tyrosine kinase inhibitors and the Glasgow Prognostic Score, an established score for inflammation, and to explore prognostic factors. METHODS: We analyzed 244 patients with stage IIIB or IV non-small-cell lung cancer in a registry, including only chemotherapy-receiving outpatients with performance status zero. RESULTS: Of 244 patients, 170 had died and the median follow-up time for the 74 surviving patients was 12.0 months. In multivariate Cox regression, smoker (hazard ratio compared to never-smoker: 1.67, P < 0.01), stage IV (hazard ratio compared to IIIB: 1.72, P < 0.01), and elevated C-reactive protein level (hazard ratio per 1 mg/dL increase: 1.08, P < 0.01) were significantly associated with shorter survival. The association between survival and smoking was significant, even after adjustment for the Glasgow Prognostic Score and regimens of chemotherapy (hazard ratio: 1.72, P = 0.02). In never-smokers, increased neutrophils were a major determinant of shorter survival and the interaction test between smoking and neutrophils was significant (hazard ratio per 1,000/mm(3) increase for smokers: 1.01; hazard ratio per 1,000/mm(3) increase for never-smokers: 1.44, P for interaction <0.01). CONCLUSIONS: Known factors including treatment response or inflammatory process are not responsible for the fact that advanced non-small-cell lung cancer patients without any history of smoking have better survival than those who have smoked.

[Training of medical team].

An appropriate cancer medicine is defined as a safe and manageable standard therapy that improves the prognosis of cancer patients. Communication and information-sharing in medical teams are essential. It is important to understand other members' work in the team, to extract multifactorial problems in the team from many points of view, and to solve problems as an entire team. In order to train medical teams from such a viewpoint, it is necessary to acquire the habit of recognizing the problems in bidirectional and solving the problems as an entire team.

A weekly combination of carboplatin and irinotecan for previously untreated extensive disease small-cell lung cancer, results of a minimum follow-up of 3 years: a multi-center Phase II trial JMTO LC02-02.

OBJECTIVE: We conducted a Phase II study to evaluate the efficacy and safety of a weekly combination of carboplatin and irinotecan regimen for patients with extensive disease small-cell lung cancer. METHODS: Patients with previously untreated extensive disease small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0, 1 or 2, were enrolled in this trial. Carboplatin area under the curve of two and irinotecan (50 mg/m(2)) were administered on days 1 and 8 every 3 weeks. Treatment was continued up to a maximum of six cycles. The expected response rate was 85%, and this regimen was considered sufficiently positive if >45 responses were observed in the 55 patients. RESULTS: Between December 2003 and September 2006, 56 patients were enrolled and 55 patients were eligible. Of 55 patients, 6 complete remissions and 37 partial remissions were achieved, and the response rate was 78.2% (95% confidence interval: 64.6-87.9). Major Grade 3 or more toxicities were leukocytopenia 3, neutropenia 15, anemia 7, infection 5, diarrhea 3, anorexia 7, nausea 6 and pneumothorax 1. The median survival was 13.9 months (95% confidence interval: 11.8-18.5) and the median progression-free survival was 5.7 months (95% confidence interval: 4.9-7.4). CONCLUSIONS: This Phase II trial of a weekly combination of carboplatin and irinotecan for extensive disease small-cell lung cancer was not positive for a response rate that is considered to be worthy of further Phase III trial.

Hyperfractionated irradiation with 3 cycles of induction chemotherapy in stage IIIA-N2 lung cancer.

BACKGROUND: The purpose of the present study was to improve the prognosis of patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). To achieve that goal, we performed induction chemoradiotherapy followed by surgery. METHODS: The criteria for this phase II study were ≤75-year-old patients with pathologically diagnosed stage IIIA-N2 NSCLC who had performance statuses of 0 or 1 with good organ function. Three cycles of chemotherapy with paclitaxel and carboplatin were carried out, with concurrent hyperfractionated irradiation (42 Gy). After re-evaluation, pulmonary resections were considered unless patients showed progressive disease. The primary endpoint was overall survival (OS), and the secondary endpoints were disease-free survival (DFS) and absence of toxicity. RESULTS: All 22 patients enrolled in this study completed the induction chemoradiotherapy without any severe complications. In these 22 patients, the 2- and 5-year OS were 81 and 47%, respectively. There were no therapy-related deaths. Surgery was subsequently performed in 19 patients (86%). Pathological complete responses were seen in 6 patients (27%), while node downstaging was obtained in 10 patients (45%). In the 19 patients who underwent surgery, the 2- and 5-year OS rates were 83 and 62%, respectively, and the 2-year DFS rate was 63%. All 6 patients with pathological complete responses survived without disease. Patients with residual multiple-station N2 showed worse OS and DFS rates than did those with downstaged and single-station N2 (P=0.026 and P<0.0001, respectively). CONCLUSIONS: This trimodal therapy was effective and well tolerated, and it is an acceptable therapeutic option for patients with locally advanced stage IIIA-N2 NSCLC. Patients without persistent multiple-station N2 showed promising survival.

Safety of erlotinib treatment in outpatients with previously treated non-small-cell lung cancer in Japan.

PURPOSE: Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor shown to provide a survival benefit for advanced non-small-cell lung cancer (NSCLC) patients. Adverse drug reactions of erlotinib in Japanese, which may be very different from those in Caucasians because of differences in genetic background, have not been fully reported. Therefore, we aimed to clarify the safety profile of erlotinib. METHODS: Forty-eight patients with pretreated NSCLC were treated with erlotinib between March 2008 and January 2009 in this historical cohort study at Kyoto University Hospital Outpatients Oncology Unit. Erlotinib 150 mg/day was administered until progressive disease or discontinuation due to adverse events. The primary endpoint was frequency and degree of adverse events, and secondary endpoints were clinical efficacy including response rate, disease control rate, progression-free survival and overall survival. RESULTS: Of 48 patients, 3 patients experienced erlotinib-induced interstitial pneumonitis, which appeared on day 15 and 70 in 2 patients who recovered and on day 8 in 1 patient who died. The incidences of pruritus, dry skin, diarrhea and stomatitis rapidly increased within 14 days after the start of medication with erlotinib. However, these adverse events were well controllable in outpatients treated with erlotinib. Overall response rate was 10% and disease control rate was 68%. The median progression-free survival was 58 days (95% confidence interval 30-118) and the median overall survival was 229 days (95% confidence interval 135-not available). CONCLUSIONS: Outpatients with NSCLC can be treated with initial administration of erlotinib by careful management.

Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201.

BACKGROUND: There is no standard chemotherapy for esophageal squamous cell carcinoma (ESCC) refractory to first-line fluoropyrimidine- and platinum-based chemotherapy. We therefore performed a randomized, selection-design phase II trial to compare docetaxel (DTX) and paclitaxel (PTX) in this setting. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive either DTX (70 mg/m2 on day 1 of each 21-day cycle) or PTX (100 mg/m2 on days 1, 8, 15, 22, 29 and 36 of each 49-day cycle). The primary end-point was overall survival (OS), and secondary end-points included progression-free survival (PFS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: Seventy-eight eligible patients (N = 39 in each group) were included for efficacy analysis. OS was significantly longer in the PTX group than in the DTX group (median, 8.8 versus 7.3 months; hazard ratio [HR], 0.62; P = 0.047). A significant benefit of PTX over DTX was also apparent in PFS (median, 4.4 versus 2.1 months; HR, 0.49; P = 0.002) and TTF (median, 3.8 versus 2.1 months; HR, 0.45; P < 0.001). RR (25.6% versus 7.7%, P = 0.065) were higher in the PTX group than in the DTX group. Compared to the PTX group, neutropenia (28% versus 80%) and leukopenia (28% versus 76%) of grade ≥3 as well as febrile neutropenia (0% vs. 46%, P < 0.0001) occurred more frequently in the DTX group. CONCLUSION: PTX showed a significantly better efficacy as well as a more manageable toxicity compared with DTX. CLINICAL TRIAL REGISTRATION: UMIN000007940.