[A case of poorly differentiated pancreatic adenocarcinoma with spontaneous regression wherein retrospective rim enhancement findings were important for diagnosis].

A 66-year-old man with epigastric pain was admitted to our hospital for further evaluation of a pancreatic mass, as indicated on transabdominal ultrasonography performed by his family doctor. Using various imaging modalities, the 22-mm tumor was diagnosed as a cystic tumor with hemorrhagic necrosis. The tumor diameter reduced to 11mm over the course of 1 month. However, the tumor margin was irregular than that at the initial diagnosis, and circumferential rim enhancement was observed in equilibrium phase computed tomography images. Therefore, we diagnosed the patient with pancreatic ductal adenocarcinoma with a necrotic component. Distal pancreatectomy with splenectomy was performed, and the subsequent histological diagnosis was poorly differentiated adenocarcinoma. This case had an interesting course as described by the diagnostic images.

Multicenter phase II study of trastuzumab with S-1 plus oxaliplatin for chemotherapy-naïve, HER2-positive advanced gastric cancer.

BACKGROUND: Trastuzumab with cisplatin and fluoropyrimidines improves overall survival (OS) in patients with HER2-positive advanced gastric cancer (AGC). S-1 plus oxaliplatin (SOX) is one of the standard regimens for HER2-negative AGC in Japan. However, few studies have evaluated trastuzumab combined with SOX in patients with HER2-positive AGC. METHODS: This was a multicenter, phase II study conducted at 10 institutions in Japan. Patients with HER2-positive AGC received S-1 twice a day on days 1-14 and oxaliplatin and trastuzumab on day 1 of a 21-day cycle. The primary endpoint was the confirmed overall response rate (ORR), and the secondary endpoints were OS, progression-free survival (PFS), and safety. The sample size was 75 to have 90% power with an alpha error of 0.1 (one-sided), expecting an ORR of 65% and threshold of 50%. RESULTS: From June 2015 to January 2018, 75 patients were enrolled. The ORR was 70.7% [95% confidence interval (CI) 59.0-80.6]. The median OS and PFS were estimated as 18.1 months (95% CI 15.6-26.5) and 8.8 months (95% CI 7.4-12.2), respectively. The major grade 3 or 4 adverse events were sensory neuropathy (16.0%) and neutropenia (10.7%). CONCLUSIONS: Trastuzumab with SOX had promising activity with well-tolerated toxicities for patients with HER2-positive AGC. CLINICAL TRIAL REGISTRATION: UMIN000017602.

A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2).

BACKGROUND: Nivolumab, an anti-programmed death-1 agent, showed survival benefits in Asian patients, including Japanese, with gastric/gastro-esophageal junction (G/GEJ) cancer. We report the analysis of the Japanese subpopulation from ATTRACTION-2 that evaluated nivolumab versus placebo in unresectable advanced or recurrent G/GEJ cancer after ≥ 2 chemotherapy regimens. METHODS: Data from the Japanese subpopulation in the randomized, double-blind, placebo-controlled, phase 3 trial were analyzed (data cutoff, February 25, 2017). Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and objective response rate (ORR). RESULTS: Among the overall study population of 493 patients, 226 (nivolumab 152; placebo 74) were enrolled from 28 sites in Japan. In the Japanese subset, median OS was longer with nivolumab versus placebo (5.4 months, 95% CI 4.6-7.4 versus 3.6 months, 95% CI 2.8-5.0). The risk of death was lower in the nivolumab versus placebo group (hazard ratio 0.58, 95% CI 0.42-0.78; p = 0.0002). Incidences of serious adverse events were 23% (35/152) and 25% (18/72) in the nivolumab and placebo groups, respectively. In the Japanese ITT population, 22% of nivolumab-treated and 28% of placebo-treated patients received prior ramucirumab treatment. Overall, clinical activity of nivolumab was observed regardless of prior ramucirumab use. In the nivolumab group, ORR and PFS were numerically higher in patients with prior ramucirumab use than in those without. CONCLUSIONS: In the Japanese subpopulation, patients receiving nivolumab had longer OS, similar to the overall population, with a manageable safety profile. The interaction between nivolumab and ramucirumab will be clarified in ongoing clinical trials.

Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G).

BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks). The primary end point was the response rate, and the secondary end points included progression-free survival, overall survival, safety, and serum biomarker levels. RESULTS: Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels. CONCLUSIONS: Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.

Phase II study of S-1 plus oxaliplatin 130 mg/m2 in Japanese patients with advanced gastric cancer.

PURPOSE: Although oxaliplatin 130 mg/m2 every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m2 (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer. METHODS: Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0-1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥ 80% relative dose intensity of oxaliplatin. RESULTS: Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8-86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1-19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9-8.5) and 13.1 months (95% confidence interval 7.4-19.0), respectively. CONCLUSION: Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.

[A case of jejunal neuroendocrine carcinoma complicated with dermatomyositis].

A 65-year-old woman who had been diagnosed with dermatomyositis presented to the hospital with a small bowel mass. She had tested positive for fecal occult blood test and anemia at a medical checkup;therefore, computerized tomography (CT) was performed at the previous hospital and it had revealed thickening of the intestinal wall. Abdominal contrast-enhanced CT, single-balloon assisted enteroscopy, and biopsy led to a diagnosis of poorly differentiated jejunal adenocarcinoma. The patient underwent laparoscopic segmental resection of the jejunum with dissection of mesenteric lymph nodes. A histological examination revealed that the tumor was neuroendocrine carcinoma (NEC), large-cell type of the jejunum, pT3, pN0, sM0, and pStage IIA. Immunohistochemically, the NEC component was positive for chromogranin A and negative for neural cell adhesion molecule and synaptophysin. The MIB-1 index was 60%. Four courses of postoperative chemotherapy using cisplatin and etoposide were administered. The patient is currently doing well without any recurrence or metastasis. To the best of the author's knowledge, this is the first report of dermatomyositis associated with primary jejunal NEC.

Chemotherapy-induced neutropenia as a prognostic factor in patients with metastatic pancreatic cancer treated with gemcitabine.

PURPOSE: Chemotherapy-induced neutropenia (CIN) is a common side effect of chemotherapy and an important dose-limiting factor. However, an association between CIN development and longer survival was recently reported in several solid cancers. In the present study, we aimed to assess whether CIN could be a prognostic factor and clarify other prognostic factors for patients with metastatic pancreatic cancer. METHODS: We retrospectively analyzed the medical records of 84 patients who received gemcitabine monotherapy as first-line chemotherapy for metastatic pancreatic cancer to assess whether CIN could be a prognostic factor. Potential prognostic factors of survival were examined by univariate and multivariate analyses using the log-rank test and Cox proportional hazard model, respectively. RESULTS: Median survival time was 170 days [95% confidence interval (CI), 147-193] in patients without CIN (grade 0), 301 days (95% CI, 152-450) in patients with grade 1-2 CIN, and 406 days (95% CI, 271-541) in patients with grade 3 CIN. The multivariate analysis revealed that a pretreatment C-reactive protein level of <0.50 mg/dL [hazard ratio (HR), 0.534; 95% CI, 0.323-0.758, P = 0.015] and grade 3 CIN (HR, 0.447; 95% CI, 0.228-0.875, P = 0.019) were independent favorable prognostic factors in patients with metastatic pancreatic cancer treated with gemcitabine. CONCLUSIONS: Neutropenia during chemotherapy was associated with increased survival of patients with metastatic pancreatic cancer. Monitoring of CIN could be used to predict treatment responsiveness.

Phase I study of highly selective inhibitor of VEGFR tyrosine kinase, tivozanib, in Japanese patients with solid tumors.

Tivozanib is a potent and selective inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases. A previous clinical trial in the EU and USA indicated that tivozanib at the maximum tolerated dose of 1.5 mg/day showed an antitumor activity in patients with renal cell carcinoma. This Japanese phase I study was designed to determine the recommended phase II dose of tivozanib for Japanese patients; secondary objectives included pharmacokinetic/pharmacodynamic profiles and preliminary efficacy. Daily treatment with tivozanib in a 3-weeks-on/1-week-off cycle was examined in nine Japanese patients with advanced solid tumors in the 3 + 3 design (Level 1, 1.0 mg; Level 2, 1.5 mg). No dose-limiting toxicity was observed throughout the study, and the maximum tolerated dose was not reached. The most commonly observed drug-related adverse events were diarrhea, dysphonia, rash, thyroid stimulating hormone increase, and with severity grade ≥3, hand-foot skin reaction, hypertension, and proteinuria. Those adverse events were generally well-manageable and mostly resolved within the tolerability evaluation period. Serum exposure to tivozanib resulted in t1/2 of more than >60 h. Increase of plasma VEGF and decrease of plasma VEGFR-1 and VEGFR-2 were observed 1-3 weeks after tivozanib treatment. Although no complete or partial response was observed, long-term stable disease continuing more than 170 days was observed in three renal cell carcinoma patients who had failed prior VEGFR inhibitors. In conclusion, 1.5 mg/day of tivozanib in a 3-weeks-on/1-week-off setting was tolerable in Japanese patients, and was recommended for further clinical trials in the Japanese population. Clinical trial Registration No: JapicCTI-090854.

Retrospective analysis of severe neutropenia in patients receiving concomitant administration of docetaxel and clarithromycin.

BACKGROUND: Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin. METHODS: Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses. RESULTS: One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia. CONCLUSIONS: This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression.

Feasibility of mFOLFOX6 as the adjuvant treatment after curative resection of metastases from colorectal cancer in Japanese patients.

BACKGROUND: An oxaliplatin-based regimen as the adjuvant treatment for stage III colon cancer demonstrated a survival advantage over fluorouracil (FU) and leucovorin (LV) in the MOSAIC and NSABP C-07 trials. For adjuvant treatment after the resection of metastases from colorectal cancer), active chemotherapy regimens such as FOLFOX are recommended. However, the safety data of FOLFOX are insufficient for its use after metastasectomy of colorectal cancer in Japanese patients. The aim of this study was to evaluate the safety of mFOLFOX6 for adjuvant treatment after the resection of metastases from colorectal cancer. METHODS: Among 67 consecutive patients who received mFOLFOX6 as the adjuvant treatment after resection of metastases from colorectal cancer between September 2002 and March 2009 in our institution, 51 patients who had not received preoperative chemotherapy were reviewed. The mFOLFOX6 treatment comprised oxaliplatin 85 mg/m(2) and l-leucovorin 200 mg/m(2) given intravenously over a 2-h period on day 1, followed by a 5-FU bolus of 400 mg/m(2) and a 46-h infusion of 5-FU 2400 mg/m(2), every 2 weeks for up to 12 cycles. RESULTS: National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTC) grade 3-4 toxicities per patient were: peripheral neuropathy 8%, allergic reaction 4%, aspartate transaminase (AST) 4%, febrile neutropenia 4%, nausea 2%, anorexia 2%, fatigue 2%, alanine transaminase (ALT) 2%, bilirubin 2%, neutrophils 49%, leukocytes 6%, and hemoglobin 2%; 71% of the patients completed the scheduled 12 cycles. CONCLUSION: Adjuvant therapy with mFOLFOX6 after resection of metastases from colorectal cancer is feasible for Japanese patients.

Comparison of safety and efficacy of S-1 monotherapy and S-1 plus cisplatin therapy in elderly patients with advanced gastric cancer.

BACKGROUND: Although S-1 plus cisplatin (SP) therapy is recognized as the standard treatment for advanced gastric cancer (AGC) in Japan, its safety and efficacy in elderly patients have not been investigated sufficiently. METHODS: We retrospectively reviewed the data of 58 patients with AGC selected from 82 consecutive patients who were ≥70 years old and were treated with SP or S-1 monotherapy as the first-line therapy. In SP, S-1 (40 mg/m(2), bid) was administered for 3 weeks and cisplatin (60 mg/m(2)) on day 8, every 5 weeks. In S-1 monotherapy, S-1 (40 mg/m(2), bid) was administered for 4 weeks, every 6 weeks. RESULTS: SP and S-1 was administered in 21 and 37 patients, respectively. There were some differences in patient characteristics between the treatment groups, such as histological type (P = 0.16); the presence of liver metastasis (P = 0.07); and the presence of peritoneal metastasis (P = 0.02). The incidences of grade 3/4 hematological toxicities were 57% (12/21) in the SP and 35% (13/37) in the S-1 group (P = 0.17). Those of non-hematological toxicities were 14% (3/21) and 14% (5/37) for anorexia, 10% (2/21) and 14% (5/37) for fatigue, and 5% (1/21) and 5% (2/37) for nausea in the SP and S-1 groups, respectively. Median progression-free survival and median overall survival in the SP and S-1 groups were 5.0 and 5.2 months, and 14.4 and 10.9 months, respectively. CONCLUSION: SP and S-1 therapy were both feasible in elderly patients, though there is the risk of a high incidence of hematological toxicities.

Enrichment of Immune-Related Genes in Aggressive Primary Breast Angiosarcoma: A Case Report.

Primary breast angiosarcoma is an extremely rare disease with a poor prognosis. Primary angiosarcoma is distinct from secondary angiosarcoma, which usually occurs in patients who have been previously treated for breast cancer. The low incidence of primary breast angiosarcoma has hindered the elucidation of its etiology and potential therapies. Here, we report a case of a patient with primary breast angiosarcoma who experienced recurrence after surgery. The tumor was refractory to systemic treatments, and the patient died 18 months after the surgery. We used RNA sequencing for gene expression profiling of the tumor. A high tumor inflammation signature score indicated enrichment in immune-related signaling. CIBERSORTx, a tool used to characterize the cellular composition of complex tissues based on gene expression, indicated that the immune cells in the tumor were predominantly macrophages, and this was confirmed using immunohistochemical analysis. These findings indicate the possible use of checkpoint immunotherapy for the treatment of primary breast angiosarcoma.

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

PURPOSE: A single 3 mg or 40 µg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 µg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. METHODS: We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. RESULTS: The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p < 0.01 for non-inferiority). CONCLUSIONS: This study showed that 1 mg granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

Leptomeningeal carcinomatosis associated with gastric cancer.

BACKGROUND: Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of gastric cancer. METHODS: The subjects were 12 gastric cancer patients who were diagnosed as having LMC at the Shizuoka Cancer Center between October 2002 and March 2009. We conducted a retrospective survey of the medical records of the study subjects and collected data on the clinical features, treatment modalities employed/outcomes, and survival of the patients. RESULTS: Of the 12 patients, 9 (75%) were male, and the median age was 63 years. Histopathologically, the majority of the patients (83%) had diffuse-type adenocarcinoma. At the time of diagnosis of the LMC, the other major sites of metastasis were the peritoneum (75%) and lymph nodes (50%). The median duration from the diagnosis of gastric cancer to the diagnosis of LMC was 15.6 months. While the treatment strategy changed with time, intrathecal chemotherapy (n = 10), followed by whole brain irradiation (n = 7) and subsequent ventriculo-peritoneal shunt (n = 3) was performed in 10 of the patients. Improvement of neurological functions was observed in 6 of the 10 patients. The median overall survival time from the diagnosis of LMC in all the 12 patients was 60 days. One patient survived for a considerably long period of 532 days. CONCLUSIONS: Multidisciplinary treatment, including ventriculo-peritoneal shunt for LMC secondary to gastric cancer, may benefit selected patients, but further accumulation of clinical cases is necessary.

Prostate cancer recurring as small-cell carcinoma with a BRCA2 somatic mutation.

Introduction: Small-cell carcinoma of the prostate has a poor prognosis, and treatment options for the refractory disease are unclear. Case presentation: A 68-year-old man with prostate cancer was referred to our hospital. He was treated with combined androgen blockade (bicalutamide and degarelix acetate). The disease progressed to castration-resistant prostate cancer, but with additional treatment, prostate-specific antigen levels remained below 0.02 ng/mL. However, computed tomography revealed enlarged right inguinal lymph nodes; moreover, his neuron-specific enolase levels were elevated. Histopathologic analysis of a biopsied lymph node confirmed small-cell carcinoma. After administering cytotoxic chemotherapy (etoposide plus cisplatin and amrubicin), the patient temporarily improved before relapsing. After genetic testing of the biopsy specimen revealed a BRCA2 deletion, we administered the oral PARP-2 inhibitor olaparib, which has achieved partial remission for 8 months. Conclusion: PARP-2 inhibition may improve the survival of patients with BRCA2-positive small-cell carcinoma of the prostate.

Risk factors and clinical courses of chemoradiation-related arterio-esophageal fistula in esophageal cancer patients with clinical invasion of the aorta.

BACKGROUND: Although concurrent chemoradiotherapy (CRT) is a standard treatment for esophageal cancer invading adjacent structures (T4-EC), arterio-esophageal fistula (AEF) occurs occasionally as a critical adverse event of T4-EC with CRT. The frequency, clinical course, and risk factors of AEF related to CRT are not well known. METHODS: We retrospectively analyzed 48 patients with T4-EC invasion of the aorta who were treated with 5-fluorouracil, cisplatin, and concurrent radiotherapy at our institution between September 2002 and April 2009. Treatment-related AEF was defined as AEF without obvious tumor progression. We evaluated the frequency, clinical courses, and risk factors of AEF. RESULTS: The median survival time was 10.6 months with a median follow-up time of 33.3 months. The 2-year survival rate was 25%. Treatment-related AEF was observed in 7 patients (14.6%) and 4 of them died of massive bleeding due to aortic AEF. In the other 3 patients with non-aortic AEF, hemorrhage could be arrested by transcatheter arterial embolization (TAE). In the univariate analysis of risk factors for AEF, lower serum cholesterol level was a risk factor for AEF (OR 14.7; 95% CI 1.58-137; P = 0.008). CONCLUSIONS: Although CRT has a curative potential even for patients with T4-EC invading the aorta, we should be aware of the relatively high incidence of treatment-related AEF. TAE may be successful in rescuing a non-aortic AEF patient. Low serum cholesterol level may be a risk factor for AEF, but further investigation is needed.

Safety and efficacy of S-1 monotherapy in elderly patients with advanced gastric cancer.

BACKGROUND: Although S-1 is effective against advanced gastric cancer (AGC), its efficacy in elderly patients has not yet been investigated sufficiently. We assessed the efficacy and safety of S-1 monotherapy in elderly patients with AGC. METHODS: We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as first-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m², on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups. RESULTS: The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respectively. In regard to nonhematological toxicities, the incidence of nausea of grade 3 or greater was 3%, 5%, and 13%; that of fatigue was 5%, 11%, and 20%; and that of anorexia was 5%, 6%, and 27%, respectively. As for the treatment efficacy, the objective response rates, median progressionfree survivals, and overall survivals in the young, middle-aged, and elderly groups were 53%, 46%, and 33%; 7.8, 5.6, and 3.9 months; and 16.9, 17.1; and 7.7 months, respectively. CONCLUSION: Although S-1 monotherapy showed moderate efficacy in elderly (≥76 years) patients with AGC, patients in this age group showed higher incidences of severe toxicities than the younger patients.

Weekly Paclitaxel after failure of gemcitabine in pancreatic cancer patients with malignant ascites: a retrospective study.

OBJECTIVES: Peritoneal metastasis is one of the major sites of disease progression of pancreatic cancer. There have been few trials in the second-line setting after gemcitabine failure because patients can hardly be candidates for chemotherapy after failure in the first-line chemotherapy, especially those with malignant ascites. The safety and efficacy of weekly paclitaxel therapy was evaluated for pancreatic cancer patients with malignant ascites in this retrospective study. METHODS: The subjects of this retrospective study were 23 advanced pancreatic cancer patients with malignant ascites who received weekly paclitaxel therapy after gemcitabine failure. Paclitaxel (80 mg/m(2), div. for 1 h) was administered on Days 1, 8 and 15, every 4 weeks. RESULTS: While the disease control rate was 35%, decrease of ascites was obtained in 30% of the patients and ascites control rate was 61%. The median survival time was 101 days. Toxicities were mild, although one treatment-related death occurred. CONCLUSIONS: Weekly paclitaxel therapy may be useful treatment option for pancreatic cancer patients with malignant ascites after gemcitabine failure.

Phase I study of docetaxel, cisplatin and S-1 in patients with advanced gastric cancer.

OBJECTIVE: S-1 plus cisplatin is standard treatment for advanced gastric cancer in Japan. Triplet therapy with docetaxel, cisplatin and fluoropyrimidine showed a survival benefit over doublet therapy, but was associated with substantial toxicities. We investigated the maximum tolerated dose of combination chemotherapy with divided-dose docetaxel added to standard-dose S-1 plus cisplatin in advanced gastric cancer patients. METHODS: Patients with advanced gastric cancer, naive to chemotherapy or not refractory to fluoropyrimidine, were enrolled. Fixed doses of S-1 (40 mg/m(2) twice daily for 3 weeks) and cisplatin (60 mg/m(2) on day 1) were administered with increasing docetaxel dose levels of 20 mg/m(2) (dose level 1), 25 mg/m(2) (dose level 2) and 30 mg/m(2) (dose level 3) on days 1, 8 and 15, or 40 mg/m(2) (dose level 4) on days 1 and 15 of a 5-week cycle. Treatment cycles were repeated until disease progression, patient's refusal or unacceptable toxicity occurred. RESULTS: Fifteen patients were enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, grade 3 febrile neutropenia was seen in one patient. At dose level 4, grade 3 infection and grade 3 abdominal pain were observed. Thus, dose level 4 was determined to be the maximum tolerated dose. The response rate was 54% (7/13), and median progression-free survival and overall survival were 243 and 383 days, respectively. CONCLUSIONS: The recommended dose of docetaxel added to standard-dose S-1 (80 mg/m(2) days 1-21) plus cisplatin (60 mg/m(2) day 1) was 40 mg/m(2) on days 1 and 15 of a 5-week cycle.