Endoscopic Chemotherapy with 5-Fluorouracil in Advanced Gastric Cancer

Introduction

It has been reported that a local injection of 5-fluorouracil (5-FU) administered endoscopically can have a favorable result in patients with early gastric cancer.

Methods

We report the application of a local injection of 5-FU administered endoscopically in three patients with advanced gastric cancer (AGC) who refused or were not suitable for surgery or systemic chemotherapy. The benefits of locally applied endoscopic chemotherapy (EC) with 5-FU as an alternative therapy were evaluated.

Results

Good tolerance with an important reduction of the tumor size and no adverse reactions was observed in all three patients.

Conclusion

EC with 5-FU is a feasible technique that can be applied in a certain group of patients with AGC. Further studies will be required to corroborate these results.     

A Case of Advanced Gastric Cancer with Poor Performance Status Which Improved by Chemotherapy

Introduction

The prognosis of advanced gastric cancer patients, especially those with poor performance status (PS), is generally dismally poor. Patients with PS 3–4 are usually ineligible for participation in clinical studies and are managed with only best supportive care. Case Report: A 63-year-old male with advanced gastric cancer was admitted to our hospital. His PS was markedly impaired (Eastern Cooperative Oncology Group PS 4), with dyspnea secondary to lymphangitis, pleuritis and pericarditis). He also had bilateral leg paralysis due to multiple bone metastases. He was treated with chemotherapy using 5-fluorouracil and leucovorin for 14 days with pericardial drainage followed by intrapericardial infusion of cisplatin. He was also treated with radiotherapy for bone metastasis. The patient required 5 l/min oxygen therapy at the start of chemotherapy, but his dyspnea was improved by day 14 and he no longer required supplemental oxygen therapy. His leg paralysis also improved with the radiation therapy. His PS was significantly improved with this multimodal treatment modality, and he was ultimately discharged with chemotherapy with oral fluoropyrimidine.

Conclusion

This case suggests that multimodal therapy including chemotherapy may be beneficial in advanced gastric cancer patients even in the setting of poor PS. Further study might be required to confirm the benefit of chemotherapy in this patient population.Key Words: Gastric cancer, Poor performance status, Chemotherapy     

Outcomes of multiple salvage chemotherapy for advanced gastric cancer: implications for clinical practice and trial design

Purpose

We analyzed the natural history of advanced gastric cancer with sequential salvage chemotherapy following first-line treatment.

Methods

We studied 532 patients with unresectable gastric adenocarcinoma who were treated at Yonsei Cancer Center (2000–2008). The patients were managed with multiple sequential salvage chemotherapy as allowed by performance status and toxicity profiles. The tumor response was assessed every two cycles.

Results

Four hundred sixty patients received palliative chemotherapy and 72 received supportive care only. The median overall survival was 12.0 months for all patients, 12.1 months for the chemotherapy group, and 2.5 months for the supportive care group (P < 0.001). In the chemotherapy group, 87% received first-line chemotherapy, 47% second-line, 23% third-line, 9% fourth-line, and 3% fifth-line. Response rates were 24.8, 12.6, 10.9, 2.6, and 0% and disease control rates were 76.3, 60.1, 54.2, 54.2, and 53.3% for first- to fifth-line treatment, respectively. The median progression-free survival was 5.5, 3.4, 2.5, 1.9, and 2.0 months and overall survival was 12.1, 7.9, 5.5, 5.0, and 6.8 months. Performance status and metastatic pattern were consistent prognostic factors throughout salvage treatment.

Conclusions

Clinical trials may be feasible in second- or third-line salvage chemotherapy for gastric cancer. Future clinical trials in these settings should take into account the low response rate, short progression-free survival, and the prognostic factors for optimal trial design.     

High Rates of Advanced Gastric Cancer in Community of Flushing, New York

Background

Gastric cancer remains a major public health issue and is a leading cause of death worldwide, accounting for 600,000 deaths annually. Over the last decades, there has been a steady decline in the incidence rates of gastric cancer. Furthermore, the incidence rates of gastric cancer in different parts of the country vary due to epidemiological and migration trends. Despite these trends, several studies that have continued to observe high rates of gastric cancer in populations that come from high-risk regions.

Aim of the Study

The aim of the study was to describe the gastric cancer patients presenting NYHQ with an emphasis on those presenting at a young age and advanced disease. A subanalysis of the Asian population was also done, which is considered a high-risk group.

Methods

Consecutive chart review of patients admitted with gastric cancer from January 2000 to August 2008 was extracted from the Oncology registry at NYHQ. Parameters that were evaluated were age, sex, race, type of gastric cancer, and stage of gastric cancer at initial presentation. The SAS/PC software package (SAS Institute Inc., Cary, NC) was employed for statistical analyses.

Results

Four hundred fifty-seven patients were diagnosed with gastric cancer. Approximately one third of the total patients were younger than 60 years of age. Of the Asian patients, almost half the patients (48.8%) had advanced disease of which two thirds were under the age of 60 years.

Conclusion

The rates of advanced gastric cancer observed at NYHQ are significant and comparable to recent epidemiology literature on rates in Asian populations in Asia. Communities, like Flushing, NY, may benefit from early detection of gastric cancers, similar to those instituted in Japan and Taiwan.     

Advanced or metastatic gastric cancer in elderly patients: clinicopathological, prognostic factors and treatments

Purpose

To analyze the clinicopathological features, prognostic factors, treatment efficacy and safety among elderly patients with advanced or metastatic gastric cancer.

Methods

Three hundred and nineteen patients aged 65 years and older, diagnosed with advanced or metastatic gastric cancer, were followed and data were retrospectively collected, reviewed and analyzed.

Results

The elderly patients carried specific clinicopathological characteristics. Body mass index (BMI), number of metastatic lesions, ascites, Karnofsky performance score (KPS), tumor differentiation grade, lactate dehydrogenase (LDH) level, local treatment, and chemotherapy were the independent prognostic factors. Serum LDH level was superior to the serum CEA level in the prognosis of advanced or metastatic gastric cancer in older patients. Cisplatin-based regimen, chemotherapy cycles, metastatic lesions, LDH level, and supraclavicular lymph node metastasis were the independent prognostic factors in 220 patients receiving chemotherapy. The toxicity was mild and tolerable.

Conclusion

KPS, BMI and a well-differentiated histopathology were factors favoring longer survival, whereas elevated serum LDH and a greater number of metastatic lesions were associated with poor prognosis among those elderly patients. Cisplatin-based chemotherapy provided survival benefits and mild toxicity.     

Phase II study of biweekly docetaxel and S-1 combination chemotherapy as first-line treatment for advanced gastric cancer

Purpose

We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.

Methods

Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0?C2 and no prior chemotherapy history were eligible for inclusion (n?=?45). Patients received a total of 215 treatment courses (median, 4; range, 2?C12) of S-1 oral administration twice daily for 1?week followed by a drug-free interval of 1?week. Docetaxel (40?mg/m²) was administered intravenously on days 1 and 15.

Results

We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3?months, the median time to progression was 6.9?months, and the median duration of response in 26 patients was 8.0?months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.

Conclusions

S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.     

Treatment of Patients with Stage IV Gastric Cancer

Purpose

Treatment of patients with stage IV gastric cancer is controversial. This study was retrospectively designed to elucidate the best treatment for these patients.

Methods

Between 2003 and 2010, a total of 558 patients with gastric cancer were treated at the Department of Surgery, Tottori University Hospital, 96 (17.2 %) of whom were diagnosed with stage IV. Among 96, 54 underwent palliative gastrectomy while 42 underwent chemotherapy, exploratory laparotomy, or gastrojejunostomy for unresectable cases. Surgical morbidity, mortality, and patient survival were analyzed with respect to several factors.

Results

Among resected cases, high age, R2 operation, and neoadjuvant chemotherapy did not increase the occurrence of postoperative complications. Patient age, R1 operation, and sufficient chemotherapy were indicated as better prognostic factors for resected stage IV gastric cancers. Even after R2 operation, continuous chemotherapy with changing regimens prolonged R2 resected patients’ survival to 25 months (mean). In unresectable cases, bypass operation did not affect patients’ survival. But, chemotherapy with changing regimens prolonged the survival of unresectable cases.

Conclusions

Adequate management can resolve surgery-related morbidity, and continuous chemotherapy may be one of the most important prognostic factors in stage IV gastric cancer.     

A phase II study of docetaxel and oxaliplatin combination in recurrent gastric cancer patients after fluoropyrimidine and/or cisplatin adjuvant treatment: a Korean Cancer Study Group Protocol ST06-02

Background

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.

Methods

Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35?mg/m²) intravenously on day 1 and 8 plus oxaliplatin (100?mg/m²) intravenously on day 1 every 3?weeks until disease progression or unacceptable toxicity.

Results

A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6?months (range, 1–48?months) were enrolled in this trial; 22 (64.7?%) patients had been exposed to both agents. Their median age was 58?years (range, 50–68?years). The overall response rate was 55.9?% (95?% confidence interval (CI), 38.3–73.5?%), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5?months (range, 9.2–50.7?months), the median progression-free survival for all patients was 5.3?months (95?% CI, 4.4–6.1?months) and the median overall survival was 13.8?months (95?% CI, 11.1–16.4?months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1?%) and diarrhea (17.6?%), respectively. Five patients (14.7?%) experienced febrile neutropenia.

Conclusions

Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.     

Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination

Purpose

Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurrent gastric cancer patients with peritoneal dissemination.

Methods

Nineteen patients with histologically confirmed unresectable or recurrent gastric cancer with peritoneal dissemination were enrolled. Oral S-1 at 80 mg/m²/day was administered twice daily for 2 weeks, followed by 1 drug-free week. Docetaxel infusion at 40 mg/m² was performed on day 1, simultaneous with S-1 administration. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary endpoints were the response rates and safety status.

Results

Patients received a median of 4 cycles of the S-1 and docetaxel regimen (range 1–43). The disease control rate was 73.7 % (14/19). Median overall survival was 459 days (15.3 months), while median time to progression was 212 days (7.1 months). Neutropenia was the most common type of toxicity (n = 7, 36.8 %).

Conclusions

Combination chemotherapy with S-1 and docetaxel is a tolerable and effective treatment for advanced or recurrent gastric cancer patients with peritoneal dissemination.     

Quality of Life in the Trastuzumab for Gastric Cancer Trial

Background.

The Trastuzumab for Gastric Cancer phase III trial demonstrated that combining trastuzumab with chemotherapy significantly improved overall survival compared with chemotherapy alone in HER2-positive advanced gastric or gastroesophageal junction cancer. We report health-related quality of life (HRQoL) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) results from this trial.

Patients and Methods.

Patients were randomized to receive six cycles of chemotherapy given every 3 weeks (capecitabine or fluorouracil, plus cisplatin) either alone or combined with administration of trastuzumab every 3 weeks until disease progression. At each clinical visit, HRQoL was assessed using two European Organization for Research and Treatment of Cancer quality of life questionnaires, QLQ-C30 and QLQ-STO22. Q-TWiST methodology was applied retrospectively using the clinical data and utility coefficients.

Results.

Trastuzumab plus chemotherapy prolonged time to 10% definitive deterioration in all QLQ-C30 and QLQ-STO22 scores, including QLQ-C30 global health status versus chemotherapy alone, from 6.4 months to 10.2 months. In addition, trastuzumab plus chemotherapy extended Q-TWiST by 2.42 months compared with chemotherapy alone.

Conclusion.

Compared with chemotherapy alone, trastuzumab plus chemotherapy prolongs time to deterioration of HRQoL and increases quality-adjusted survival in patients with HER2-positive gastric or gastroesophageal junction cancer.     

Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study

Background

The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2) positive advanced/metastatic gastric or gastroesophageal junction cancer. ToGA showed that trastuzumab plus chemotherapy (capecitabine/cisplatin or 5-fluorouracil/cisplatin) improved overall survival in the overall population (hazard ratio 0.74). Regional differences in outcome in favor of Japanese populations were observed in other studies; therefore, subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients.

Methods

We performed subgroup analyses on 101 Japanese patients enrolled into ToGA (trastuzumab plus chemotherapy, n?=?51; chemotherapy, n?=?50).

Results

Median overall survival in the Japanese subgroup was 15.9?months (95% confidence interval 12–25) for trastuzumab plus chemotherapy and 17.7?months (95% confidence interval 12–24) for chemotherapy (hazard ratio 1.00; 95% confidence interval 0.59–1.69). After adjusting for prespecified covariates, the estimated hazard ratio for overall survival was 0.68 (95% confidence interval 0.36–1.27). Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios.

Conclusions

After adjusting for imbalanced patient backgrounds between arms, overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone.     

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

Background

The standard of chemotherapy regimens for advanced or metastatic gastric cancer and the clinical outcome were heterogeneous in Asian versus non-Asian countries. This study aimed to explore predictors of safety and efficacy of chemotherapy for patients with advanced or metastatic gastric cancer.

Methods

Treatment group-based meta-analysis and meta-regression were performed to analyze results of randomized trials published since 2005 for advanced or metastatic gastric cancer patients who received systemic chemotherapy as first-line treatment. Data were extracted and synthesized according to the Cochrane guidelines.

Results

Twenty-five trials (8 Asian, 17 Western or international) with 56 treatment groups were analyzed. Asian trials reported a lower percentage of gastroesophageal junctional carcinoma, higher percentage of diffuse-type histology, and more frequent use of second-line chemotherapy. Meta-analysis revealed significant heterogeneity both in treatment safety (grade 3–4 neutropenia and diarrhea) and efficacy [6-month progression-free survival (PFS) and 1-year overall survival (OS)]. Meta-regression analyses indicate that Asian trials are associated with an 8.2% lower incidence of grade 3–4 neutropenia and 2.1% lower incidence of grade 3–4 diarrhea. A lower percentage of patients with gastroesophageal junction carcinoma and the use of combination regimens predicted better PFS. The use of second-line chemotherapy predicts better 1-year OS, which will increase by 10% for every 10% increase in patients who received second-line chemotherapy.

Conclusion

Geographic region (Asian vs. non-Asian) is an independent predictor of safety in systemic therapy for gastric cancer.     

Therapie des fortgeschrittenen Magenkarzinoms

Context

In the metastatic setting treatment goals are palliative. Chemotherapy can prolong survival, improve symptoms and can help to maintain a better quality of life.

Objective

The aim of this study was to discuss the new treatment options and the existing results in advanced gastric cancer.

Material and methods

Treatment recommendations are given in consideration of updated literature (Pubmed, MEDLINE and manual search).

Results

Combination chemotherapy including a platinum compound and a fluoropyrimidine are regarded as the gold standard of care. Oxaliplatin can substitute for cisplatin while capecitabine or S1 can substitute for infusional 5-FU. In elderly patients oxaliplatin has advantages compared with cisplatin. Triplet combinations containing a platinum salt, a fluoropyrimidine and a taxane or (with less evidence) an anthracycline are more efficacious but also expose patients to more side effects. Second line chemotherapy is indicated for patients who progress during or after first line chemotherapy. The monoclonal antibody trastuzumab has been shown to prolong survival when combined with cisplatin and 5-FU or capecitabine in gastric cancer patients with overexpression of the growth factor HER2.

Conclusion

The therapeutic options for advanced gastric cancer have significantly increased. Presently, there are several effective treatment regimens available.     

Transient Elastography for the Prediction of Oxaliplatin-Associated Liver Injury in Colon Cancer Patients : A Preliminary Analysis

Objective

The prognosis of advanced colon cancer has improved significantly over the last decade since new chemotherapy regimens including oxaliplatin have been developed. However, oxaliplatin-induced liver injury and characterized hepatic hemostatic status can occur after chemotherapy. The assessment of this type of liver injury is often difficult.

Methods

Elastography (Fibroscan?) was used to evaluate liver injury in five cases before and after 5-FU, leucovorin, and oxaliplatin combination (FOLFOX) treatment.

Results

A clear change was observed in the stiffness of liver after chemotherapy within 48 h, and the hepatic stiffness was normalized in most cases after 2 weeks. Among the five patients, one patient showed aberrant elevation after a FOLFOX treatment, and the patient showed liver injury pathologically.

Conclusion

Elastography is a good tool for evaluating hepatic injury after FOLFOX treatment.     

Predictive factors for the efficacy of cetuximab plus chemotherapy as salvage therapy in metastatic gastric cancer patients

Purpose

We performed a retrospective study to evaluate the efficacy of cetuximab plus chemotherapy in metastatic gastric cancer (MGC) patients previously treated with chemotherapy and to investigate potential predictors of treatment efficacy in those patients.

Methods

Thirty-two patients with MGC were included in this study. Cetuximab was delivered, often combined with irinotecan-based chemotherapy. Thirty patients were analyzed for K-ras mutations via direct sequencing of the tumor DNA.

Results

Patients were heavily pretreated with a median number of three previous lines of palliative chemotherapy (56% of the patients were refractory to all of the following drugs: fluoropyrimidines, cisplatin, irinotecan, oxaliplatin, and docetaxel) and 53% of the patients displayed poor performance status. Of 28 response-assessable patients, the overall response rate to cetuximab plus chemotherapy was 3.6% [95% confidence interval (CI) 0–10.5%] and the disease control rate was 28.6%. The median progression-free survival (PFS) was 1.7 months (95% CI 1.3–2.1 months), and the median overall survival (OS) was 3.2 months (95% CI 1.4–5.0 months). Multivariate analyses revealed that skin rash and performance status were significantly associated with PFS and OS. The presence of a K-ras mutation (13.3%) was not associated with either PFS or OS.

Conclusion

Our study suggests that MGC patients with good performance status and skin rash benefit most from salvage cetuximab combined with chemotherapy, even in heavily pretreated status.     

Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysis

Background

It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy.

Methods

We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy.

Results

In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1?months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4?months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8?months, and the median overall survival (OS) was 12.2?months. Compared with patients with an RFI of <6?months (n?=?25), patients with an RFI of ≥6?months (n?=?27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2?months, respectively), and longer overall survival (7.3 vs. 16.6?months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6?months was still significantly associated with PFS and OS.

Conclusions

S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6?months.     

Lapatinib acts on gastric cancer through both antiproliferative function and augmentation of trastuzumab-mediated antibody-dependent cellular cytotoxicity

Background

Trastuzumab has been recently approved for clinical use to treat HER2-expressing advanced gastric cancer, and anti-HER2-targeting therapy has become a promising option for gastric cancer. Lapatinib is a dual tyrosine kinase inhibitor targeting EGFR and HER2. The aim of the present study was to explore the utility of lapatinib for gastric cancer, with a particular focus on trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC).

Methods

Nine gastric cancer cell lines were evaluated for the effects of lapatinib on the cell-surface accumulation of HER2 and analyzed for their additional effects on trastuzumab-mediated ADCC. Also, HER2 signaling with Western blot, proliferative function with the MTT assay, and apoptosis-inducing activity with 7ADD/Annexin-V were investigated when a panel of gastric cancer cell lines was treated with lapatinib.

Results

Lapatinib inhibited HER2 signaling and cell proliferation in the panel of gastric cancer cell lines. Lapatinib also induced the accumulation of HER2 on the cell surface, resulting in the enhancement of trastuzumab-mediated ADCC of gastric cancer.

Conclusions

Lapatinib exhibits inhibitory activity in gastric cancer cells, and the combination of lapatinib with trastuzumab may be a promising treatment strategy for gastric cancer patients.     

Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines,platinum, and taxanes

Background

Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan.

Methods

A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes.

Results

Between February 2008 and December 2013, 52 patients received third-line irinotecan monotherapy. Among the 32 patients with measurable lesions, 1 patient achieved a confirmed partial response and 6 patients had stable disease. The overall response rate was 3% and the disease control rate was 22%. Median progression-free survival was 2.3 months [95% confidence interval (CI), 1.8–2.8] and median overall survival was 4.0 months (95% CI, 2.6–5.3). The most common adverse events of grade 3 severity or higher were neutropenia (27%), febrile neutropenia (12%), anorexia (12%), and diarrhea (6%). Although no treatment-related deaths occurred, 2 patients (4%) died of disease progression within 30 days after the last administration of irinotecan.

Conclusion

Irinotecan monotherapy appears to be tolerated but was shown to have modest activity as third-line chemotherapy for advanced gastric cancer.

     

A Case Report of Gemcitabine Treatment for Duodenal Cancer: The Good (A Sustained Response) and The Bad (Life Threatening Refractory Thrombotic Thrombocytopenic Purpura)

Introduction

Adenocarcinoma of the duodenum is a rare cancer and not submitted to the type of clinical trials that guide chemotherapy treatments in other gastrointestinal malignancies.

Case Report

This case demonstrates the potential use for gemcitabine, a chemotherapy typically used in pancreas and biliary tract tumors, in this difficult to treat disease as this patient had a partial response to single agent gemcitabine. Unfortunately, this case also demonstrates one of the rare potential adverse reactions to gemcitabine, which is the development of thrombotic thrombocytopenic purpura (TTP).

Conclusion

In this case, the TTP was extremely difficult to treat but was resolved with splenectomy.     

Safety, efficacy and pharmacokinetics of S-1 in a hemodialysis patient with advanced gastric cancer

Purpose

The safety and efficacy of S-1 in hemodialysis patients have not been established. We evaluated the safety and efficacy and pharmacokinetics of S-1 in a hemodialysis patient with advanced gastric cancer.

Patient

A 66-year-old Japanese man with chronic renal failure, who had undergone hemodialysis three times a week for 3 years. Based on the diagnosis of stage IV gastric cancer, S-1 therapy was started. S-1 was administered 11 times at a daily dose of 23.5 mg/m² (40 mg/body) after hemodialysis, followed by a rest. One course was a period of 28 days. Blood samples were obtained after the first administration of S-1 and before beginning the fourth course. The concentration of 5-FU was determined by high-performance liquid chromatography.

Results

Area under the concentration–time curve (AUC) of 5-FU was 2647.2 ng h/mL after administration of S-1 of 23.5 mg/m² (40 mg/body). During the S-1 treatment, serious adverse events such as neutropenia were not observed; however, decreases in hemoglobin level were observed (grade 3). The treatment was well tolerated. After the second course of chemotherapy, the primary lesion showed a partial response and lymph node metastases and liver metastases showed stable disease.

Conclusions

Our results suggest that S-1 is an important treatment option for patients with hemodialysis with advanced gastric cancer.