Izumi Ohno

Twenty-six cases of advanced ampullary adenocarcinoma treated with systemic chemotherapy.

OBJECTIVE Ampullary adenocarcinoma is a rare disease entity and little information regarding these tumors is available. The aim of the present study was to clarify the treatment outcome of systemic chemotherapy in patients with advanced ampullary adenocarcinoma. METHODS This study consisted of a retrospective review of data obtained from patients diagnosed as having advanced ampullary adenocarcinoma who received non-surgical treatment at a single institution between 1997 and 2010. RESULTS We identified 26 patients (15 men, 11 women; median age, 62.0 years) who received treatment for advanced ampullary adenocarcinoma. Twelve patients had Stage IV disease and 14 had recurrences. The chemotherapy regimens consisted of 5-fluorouracil-based regimens (5-fluorouracil + cisplatin, n = 3; tegafur-uracil + doxorubicin, n = 5 and tegafur, gimeracil and oteracil potassium, n = 3) and gemcitabine-based regimens (gemcitabine, n = 10 and gemcitabine + cisplatin, n = 5). The overall response rate was 7.7%. The median progression-free survival period was 3.2 months (2.5 months in the 5-fluorouracil group vs. 3.5 months in the gemcitabine group), and the median overall survival time was 9.1 months (8.0 months in the 5-fluorouracil group vs. 12.3 months in the gemcitabine group). The median overall survival was significantly longer in stage IV disease than in recurrent disease. The histological phenotype was determined in 10 of the 26 patients. Eight patients had intestinal-type adenocarcinomas and remaining two patients had pancreatobiliary-type adenocarcinomas. CONCLUSIONS The treatment outcome of patients with advanced ampullary adenocarcinoma was poor. Further development of novel treatments is necessary to improve the prognosis.

Successful Everolimus Treatment in a Patient with Advanced Pancreatic Neuroendocrine Tumor Who Developed Everolimus-Induced Interstitial Lung Disease on Two Occasions: A Case Report

Chemotherapy-associated interstitial lung disease (ILD) is often fatal, and the chemotherapeutic regimen generally cannot be resumed. ILD associated with the mammalian target of rapamycin (mTOR) inhibitor everolimus has many features distinct from chemotherapy-associated ILD. We present the case of a 58-year-old woman with an advanced pancreatic neuroendocrine tumor with liver metastases, in whom everolimus treatment was maintained and resulted in a partial response despite two occurrences of everolimus-induced ILD during a 31-month treatment period until disease progression. Physicians treating with everolimus should monitor patients closely for ILD and should apply appropriate management strategies to optimize the possibility of maintaining everolimus therapy.

Influence of obstructive jaundice on chemotherapy in patients with unresectable biliary tract cancer.

336 Background: The aim of this study was to investigate the influences of obstructive jaundice (OJ) in unresectable biliary tract cancer (BTC) patients. Methods: Data of a total of 200 patients who were newly diagnosed as having unresectable BTC and received chemotherapy between July 2006 and December 2012 were retrospectively reviewed. Patients were divided into two groups according to whether or not they presented with OJ as the incipient chief complaint (Group 1, patients with OJ; Group 2, patients without OJ). Results: There were 81 patients in Group 1 and 119 patients in Group 2. In regard to the primary site (Group 1/Group 2), 29 had perihilar (27/2), 7 had distal (7/0), 68 had intrahepatic (15/53), 92 had gallbladder (31/61) and 4 had ampulla of vater (1/3) (p<0.01). The rate of distant metastasis was 60% in Group 1 and 76% in Group 2 (p=0.02). The performance status was good (0 or 1) in 96% of cases of both the groups. There were no significant differences in the median survival time between Grou...

Efficacy of prophylactic minocycline treatment for skin toxicities induced by erlotinib plus gemcitabine in advanced pancreatic cancer patients.

266 Background: Erlotinib has been reported to be associated with a high incidence of skin toxicities, such as acneiform rash, paronychia and xerosis. The aim of this study was to evaluate the efficacy of prophylactic minocycline treatment for the skin toxicities induced by erlotinib, as compared to deferred minocycline treatment. Methods: The study subjects were patients with advanced pancreatic cancer receiving treatment with erlotinib plus gemcitabine. In the prophylactic minocycline group, oral minocycline was administered at the dose of 200 mg/daily during the chemotherapy prior to the emergence of any skin toxicities, while in the deferred minocycline group, oral minocycline treatment at 200mg/daily was initiated after the emergence of grade 2-3 of skin toxicities. In both groups, heparinoids were administered during the chemotherapy and topical steroid therapy was initiated after the emergence of the skin toxicities. Results: A total of 96 patients were enrolled, of which 44 received prophylactic m...

Early Relapse of Unresectable Gallbladder Cancer after Discontinuation of Gemcitabine Monotherapy Administered for 5 Years in a Patient Who Had Complete Response to the Treatment

The tumor shrinkage effect of gemcitabine is considered to be limited in cases of advanced gallbladder cancer, and there are few reports of complete response to gemcitabine therapy in patients with this cancer. Therefore, the treatment continuation strategy in these patients, after a complete response has been achieved, still remains to be established. Here, we present the case of a 77-year-old patient with unresectable gallbladder cancer, who after showing complete response to gemcitabine monotherapy administered for 5 years, showed early relapse within only 11 months of discontinuation of the drug. Thus, it is necessary to establish a suitable treatment continuation strategy for patients who show complete response to gemcitabine treatment.

Association of hypophosphatemia-occurring sorafenib with prognosis and hepatic impairment in patients with advanced hepatocellular carcinoma.

188 Background: Hypophosphatemia is observed during sorafenib treatment. At the increased metabolic demand of the liver, hypophosphatemia is considered to be associated with a good clinical course. Hypophosphatemia associated with sorafenib treatment may also be a favorable event, but this has not yet been elucidated. The aim of this study was to evaluate the clinical significance of hypophosphatemia developing during sorafenib treatment for advanced hepatocellular carcinoma (HCC). METHODS The data of 41 advanced HCC patients (median age: 68 years, female/male: 4/37, HBs-Ag(+)/HCV-Ab(+):10/22) who received sorafenib treatment (800 mg, daily) for more than 30 days were reviewed. There were 27 and 14 patients with Child-Pugh class A and B. UICC stage II/III/IV was observed in 13/10 /18 patients. Clinical data, including those on the serum level of inorganic phosphate (IP), were collected before and after 30 days of sorafenib treatment. Overall survival time (OS) was calculated from the start of sorafenib treatment. The significance level was set at p<0.05. RESULTS Mean serum IP level before sorafenib treatment was 3.2mg/dL (range 2.4-4.5). After 30 days treatment, IP level was decreased (mean 2.6mg/dL, range 1.3-3.9), compared to that at pre-treatment (p<0.001). The patients in whom the serum IP was less than 2.4mg/dL at 30 days was assigned to the decreased IP group (N=14, mean IP 2.1mg/dL, range1.3-2.3). The decreased IP group showed a better prognosis (no event of death during the observation time) than the nondecreased IP group (MST 286 days, p=0.024). In the non-decreased IP group, the serum Alb (mean 3.6g/dL) and T.Bil (mean 0.8mg/dL) were worse after 30 days treatment (Alb 3.4g/dL p=0.007, T.Bil 1.1mg/dL p=0.037). However, deterioration of Alb (mean 3.7 vs. 3.6g/dL p=0.505) and T.Bil (mean 0.7 vs. 0.8mg/dL p=0.404) could be avoided in the decrease IP group. CONCLUSIONS Hypophosphatemia occurring during sorafenib treatment for advanced HCC was associated with a favorable prognosis. The serum Alb and T.Bil levels were indicators of liver function and were preserved in patients with decreased serum levels of phosphate. No significant financial relationships to disclose.

Clinical significance of elevation of the serum IL-6 level in patients with advanced pancreatic cancer.

181 Background: IL-6, one of the pro-inflammatory cytokines, is a recognized mediator of cachexia and cancer cell invasion. It has been reported that elevation of the serum IL-6 level may be associated with deterioration of the clinical condition and tumor progression in advanced pancreatic cancer (PC) patients. The aim of this study was to clarify the clinical features of increased serum IL-6 levels in patients with advanced PC receiving chemotherapy. METHODS Patients with treatment-naïve unresectable PC and no obvious infectious conditions were eligible for this study. Serum levels of IL-6 were measured by an electrochemiluminescence assay. Symptoms were rated numerically from 0 to 10 using the Japanese version of the M. D. Anderson Symptom Inventory. Tumor volume was calculated as the sum of the long diameters of the tumors. The measurements were performed before chemotherapy and at one month after the start of chemotherapy. RESULTS A total of 87 patients (male/female: 41/46; ECOG performance status: 0/1/2: 59/26/1; media age: 66 years) were enrolled; all patients were administered systemic chemotherapy (gemcitabine [GEM]/GEM+S-1/GEM+other/S-1: 52/11/9/15). The median serum level of IL-6 was 1.3 pg/mL before chemotherapy (at baseline) and 1.8 pg/mL at one-month after the start of chemotherapy. The median change of IL-6 from the baseline was +0.18 pg/mL. Patients with increase of the serum IL-6 level by more than 0.18 pg/mL were assigned to the elevated IL-6 group (n=42; median change in IL-6: +1.66 pg/mL). The elevated IL-6 group showed more sadness (p=0.019), numbness (p=0.008), and gain of body weight (p=0.016) at the baseline as compared to the non-IL-6-elevated group (n=42; median change in IL-6: -0.27 pg/mL). Comparison of the elevated and non-IL-6-elevated groups revealed a greater degree of increase in the tumor volume (p=0.015), deterioration of nausea (p=0.046) and vomiting (p=0.028), neutrophilia (p=0.004), and elevation of the serum C-reactive protein (p=0.011) in the elevated IL-6 group than in the non-IL-6-elevated group. CONCLUSIONS Elevation of the serum IL-6 level may be associated withsymptom deterioration, increase of the tumor mass, and inflammatory reaction in patients with advanced PC. No significant financial relationships to disclose.