Metastatic Gastric Adenocarcinoma Research Articles

Oxaliplatin, irinotecan, and bevacizumab followed by docetaxel and bevacizumab in inoperable gastric cancer: First results of a multicenter phase II trial (AGMT Gastric-3) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT).

e14502 Background: Patients (pts.) with advanced gastric cancer still have only limited treatment options. In our previous phase II trials (AGMT-Gastric-1 and AGMT Gastric-2) we could show efficacy of oxaliplatin and irinotecan as well as oxaliplatin, irinotecan and cetuximab.Time to progression however was short suggesting resistancy to chemotherapy. Therefore in the current Gastric-3 trial we investigate sequential chemotherapy combined with bevacizumab. Methods: Oxaliplatin 85 mg/m2 biweekly (q2w) and irinotecan 125 mg/m2 q2w were administered for the first three months followed by docetaxel 50mg/m2 q2w for three months. Chemotherapy is combined with bevacizumab 5 mg/kg q2w until progression. Inclusion of 40 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma is planned in a first line setting. For this abstract 19 patients have been evaluated: Median age: 65 years (range 26-81 years), PS 0: 13 patients, PS 1: 5 patients (1 patient not available), single metastatic site: 13 patients, multiple metastases: 6 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 (90%) and included nausea (9/19), polyneuropathy (8/19), diarrhoea (8/19), fatigue (7/19), asthenia (4/19) and vomiting (4/19). There were 4 adverse events (AEs) grade 4, all in one patient, three consecutive cases of neutropenia and one leucopenia. There were 8 AEs grade 3 in 6 patients including thrombocytopenia, anemia, leucopenia, neutropenia, hydronephrosis, candidiasis, duodenitis with diarrhea and haematemesis (one case each). Conclusions: The combination of oxaliplatin and irinotecan with bevacizumab followed by docetaxel with bevacizumab is feasible and safe in advanced gastric cancer. Updated results will be presented during the meeting.

Correlation of high FDG uptake in PET/CT with poor prognosis in metastatic gastric adenocarcinoma.

e14668 Background: Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. 18F-FDG PET may have a role in predicting patient prognosis on the basis of the metabolic activity of primary tumors (PT). We retrospectively evaluated prognostic value of FDG-PET/CT in metastatic gastric cancer. Methods: This was a retrospective analysis of 75 patients with metastatic G who attended chemotherapy units of the participating centers from January 2007 to June 2010 and underwent FDG PET/CT imaging before the first line chemotherapy. Results: Median age in our study group was 62 and 25 of them were women. Median follow-up was 10 months. The patients received either ECF (n=16) or TCF (n=47) or cisplatin and capesitabine (n=12). Both PFS and OS were significantly higher in the ECOG PS 0 and 1 group of patients (n=58) compared to ECOG PS 2 (n=17; 6 vs 4 months, p= 0.032) and 13 vs 8 months, p= 0.002 respectively). 57 patients were adenocarcinoma while signet ring cell type were diagnosed in 18 patients. Median PFS and OS were 5 and 11 months respectively. Median SUV max value (>8.6) for the PT was significantly associated with both PFS (6 vs 4 months, , p= 0.04, HR: 0.45 (0.21-0.98) and OS (16 vs 8 ay, HR: 0.40 [0.17-0.90] p= 0.03). Median highest SUV max value (>7) for distant metastasis (DM) was not correlated with PFS (p= 0.7) and OS (p= 0.1). When the correlation between median SUV max for each metastatic site with PFS and OS were assessed, only liver metastasis had a significant association with OS; (15 vs 7.5 months, HR: 0.18 [0.07-0.46] p= 0.0003). In multivariate analysis ECOG PS (p=0.0015), SUV max of the primary tumor sites (p=0.02) and metastatic liver lesions (p= 0.00001) remained as significant predictors for poor OS. Conclusions: In metastatic gastric cancer PET CT is a useful instrument for predicting poor prognosis. High FDG uptake of primary tumor site and metastatic liver lesions are significantly associated with shorter OS.

Results of docetaxel plus oxaliplatin (DOCOX) with or without cetuximab in patients with metastatic gastric and/or gastroesophagel junction adenocarcinoma: Results of a randomized phase II study.

4015 Background: Advanced adenocarcinoma of the gastroesophageal junction and/or stomach is standardly treated by combination chemotherapy with minimal improvements in survival. This study evaluated the value of adding cetuximab (C) to combination chemotherapy in this disease. Methods: The primary objective of this noncomparative study was progression-free survival (PFS); secondary objectives were 1-yr survival, response rate, time to response (TTR), duration of response (DOR), and safety. Treatment (Tx): Arm 1: DOCOX = docetaxel 60 mg/m2 plus oxaliplatin 130 mg/m2 on Day 1 of each 21-day cycle. Arm 2: DOCOX + C = DOCOX with C 400 mg/2 1st dose, then 250 mg/m2weekly. Key inclusion: stage IV adenocarcinoma of the GEJ/stomach; measurable disease; ECOG 0-2; and normal renal, hepatic, and marrow function; exclusion: any prior Tx other than adjuvant radiation with 5-FU/leucovorin. Results: 150 pts enrolled; 75/arm. Demographics Arm 1/2: male 79%/80%, median age 61/64 yrs; disease site: gastric 44%/41%, GEJ 51%/55%, both 5%/4%; 93%/96% had surgery, 7%/5% had radiation. Response rates/arm: 24%/29%. Median PFS was 4.7/5.1 mos (ranges, <1-24.8/<1-10.4); 1-yr survival was 40%/32%, median overall survival was 9.0/8.5 months; median TTR was 1.3/1.3 mos, and median DOR was 13.8/7.2 mos. The most frequent grade 3-4 treatment-related adverse events (AEs) included: neutropenia (44%/40%) diarrhea and febrile neutropenia (12%/17%, each), and fatigue (10%/15%). Analysis of KRAS is ongoing. Conclusions: The addition of C to DOCOX may improve RR minimally; there appears to be no significant improvement in PFS, OS, or 1-year survival. C did not produce clinically significant benefit when added to the backbone of DOCOX. Toxicities were consistent with the known safety profiles of the study drugs. Supported in part by grants from sanofi-aventis, Bridgewater, NJ and Lilly/ImClone, Indianapolis, IN.

Phase II study of trastuzumab and cisplatin as first-line therapy in patients with HER2-positive advanced gastric or gastroesophageal junction cancer

HER2 over-expression and/or amplification are present in 9-38% of gastric or gastroesophageal junction (GEJ) cancers and are correlated to poor outcome. We conducted a multicentre phase II trial to evaluate trastuzumab in combination with cisplatin in patients with untreated HER2-positive advanced gastric or GEJ cancer. Chemo-naïve patients with measurable, non-resectable, advanced or metastatic gastric or GEJ adenocarcinoma, with HER2 over-expression and/or amplification (IHC 3+, or IHC 2+ and FISH+), age ≥18 years, ECOG ≤2, left ventricle ejection fraction ≥50% and adequate organ function were eligible. Treatment consisted of trastuzumab (8 mg/kg on cycle 1 day 1 as loading; 6 mg/kg in subsequent cycles) and cisplatin (75 mg/m(2)), both intravenously on day 1, every 21 days. Twenty-two out of 228 patients (10%) were HER2- positive and were included in this phase II trial. The median age was 66 years and ECOG 0/1 was 41%/59%. The median number of cycles was 4 (range 1-41). The confirmed ORR was 32% and disease control was achieved in 64% of patients. Median time to progression was 5.1 months. Grade 3 adverse events included asthenia (27%), neutropenia (18%), anorexia (14%), diarrhoea (9%) and abdominal pain (9%). There were no grade 4 toxicities or treatment-related deaths. Higher baseline HER extracellular domain (ECD) levels were associated with better outcome in terms of response and survival. Trastuzumab in combination with cisplatin is an active regimen and has a favourable toxicity profile in advanced HER2-positive gastric or gastroesophageal cancers.

Metastatic gastric adenocarcinoma primarily presenting in the fallopian tube

We report a 48-year-old woman presenting with gastric adenocarcinoma metastatic only to the left fallopian tube. In addition to invasive, poorly differentiated adenocarcinoma, there were areas simulating intraepithelial carcinoma, suggesting a primary fallopian tube lesion. The differential diagnosis included a metastatic process, based on unusual morphologic patterns with occasional signet-ring cells, single-cell linear pattern of infiltration, and abundant lymphvascular space invasion. Metastasis from an upper gastrointestinal primary was confirmed by immunostains (cytokeratin 7, CDX-2, and p53 positive in the tumor cells and cytokeratin 20, WT-1, estrogen, and progesterone receptors negative). Imaging studies and a posterior biopsy demonstrated primary gastric adenocarcinoma with similar histology and immunoprofile. We report an unusual case of primary gastric adenocarcinoma presenting only in the fallopian tube and discuss its mimics and differential diagnosis.

A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models

To make up for the limitations of previous prognostic models, we developed and validated a model in patients with metastatic or recurrent gastric adenocarcinoma (AGC), and to compare with previous models. A total of 2,805 patients received chemotherapy for AGC in Asan Medical Center between January 2000 and December 2008 and were randomly split into training and validation sets of 1,870 and 935 patients, respectively. A prognostic model was developed from the training set. The median follow-up duration was 26.5months (range, 10.8-116.3), during which time 2,495 patients (88.9%) died. Eight factors associated with poor prognosis were identified by multivariate analysis: ECOG performance status ≥2 (2 points), no gastrectomy, peritoneal metastasis, bone metastasis (2 points), lung metastasis, alkaline phosphatase>120IU/l, albumin<3.3g/dL, and total bilirubin>1.2mg/dL. A prognostic model was developed by dividing patients into good (0-1 points), moderate (2-3), and poor (≥4) risk groups. The overall survival (OS) curves for three risk groups differed significantly for both the training and the validation sets (P<0.001 each). In the training set, the median OS for the three risk groups was 14.0, 9.4, and 5.1months, respectively. Application of three previous prognostic models to our validation set showed that the four models, including ours, had similar ability to predict survival outcomes (c-statistics, 0.5520-0.5836). Validation and comparison of prognostic models indicated that our model was as effective as the previous models to stratify the patients with AGC.

Palliative resection for stage IV gastric cancer.

148 Background: Metastatic gastric adenocarcinoma is an incurable condition and little progress has been made in its treatment. The role of palliative surgical resection is still debatable. Methods: We retrospectively evaluated the efficacy of palliative gastrectomy for treating incurable gastric cancer. In our institution 51 cases were found to have incurable tumors at laparotomy and received palliative gastrectomy from 2003 through 2009. In the analysis, particular attention was paid to the prognostic factors of age, tissue type (diffuse type and intestinal type), metastatic site (liver, peritoneal and lymph node) and postoperative chemotherapy. Results: One-year survival rate of all patients was 58% and the median survival time was 23.5 months. The median survival time was significantly greater in patients undergoing chemotherapy group than in those not undergoing chemotherapy (24.0 versus 9.4 months; p=0.016). Conclusions: Long-term survival for patients with stage IV gastric cancer who are managed with surgical resection and chemotherapy is achievable. Further study with a larger number of patients is warranted. No significant financial relationships to disclose.

Pharmacokinetic and pharmacodynamic analysis of gastric cancer patients treated with telatinib.

113 Background: The soluble form of the VEGFR2 receptor (sVEGFR2) neutralizes circulating VEGF, and functions as a negative feedback mechanism to enable partial inhibition of VEGF-stimulated endothelial cell migration and proliferation. In response to inhibition of VEGFR2 tyrosine kinase activity, up-regulation of VEGF expression and down-regulation of sVEGFR2 expression levels have been observed (Murukesh et al., 2010). Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Correlation between telatinib exposure and reduction in plasma sVEGFR2 levels from baseline has previously been demonstrated in patient serum samples in phase I studies. Methods: TEL0805, a phase II study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Patient serum samples were obtained on day -7, [6 plasma samples (pre-dose, and at 30 min, 1, 2, 3 and 4 hours)] and on day 1, [4 plasma samples (pre-dose and at 1, 2 and 3 hours)] and evaluated for the levels of telatinib and its M2 metabolite (M2). Additional serum samples were collected every 42 days and evaluated for VEGF and sVEGFR2 levels. Results: Measurement of tel and M2 levels confirmed previous pharmacokinetic findings and demonstrated no drug accumulation following continuous daily dosing. Baseline plasma sVEGFR2 levels have previously not been reported for advanced gastric cancer patients and displayed a wide range at disease presentation. Reduction in sVEGFR2 levels were noted for nearly all treated patients and correlated with the duration of stay on tel therapy. Conclusions: Telatinib continuous dosing is possible in combination with XP with little effect on tel exposure or accumulation. Reduction in sVEGFR2 levels may be useful in identifying patients who may benefit from tel treatment in this combination setting. [Table: see text]

Onset of CT scan morphological changes in metastatic lesions and associated responses in gastric patients treated with telatinib.

81 Background: Response to the antiangiogenic agent, bevacizumab, by CT has been associated with a unique morphologic change in liver metastasis (mets) where heterogeneous attenuation, variable degree of enhancement and ill-defined borders before treatment transform into homogeneous, hypoattenuating lesions with well defined borders, mimicking a cyst. CT-based morphologic criteria in colorectal cancer (CRC) had a statistically significant association with pathologic response and overall survival, (Chun, JAMA 2009). The CT changes likely reflect the replacement of mets by fibroconnective tissue rather than tumor necrosis. Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Methods: TEL0805, a Phase 2 study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Response assessments were every 2 cycles (6 weeks). The ORR in response evaluable pts was 69% (1 CR, 21 PR in 32 pts). CT films from 16/32 response evaluable pts were analyzed and reviewed by a radiologist at a single institution, 10 pts had liver mets. Results: The median onset of response was 49 days. CT changes of mets at week 6 scans included: decreased attenuation and/or a sharp interface with rapid reduction of mets (n=6); mixed response, with decreased attenuation but persistent borders, and/or slight increase in mets followed by onset of response week 12 (n=3), and PD (n=1). CT changes correlate with durable responses. Conclusions: Telatinib + XP produces rapid onset of tumor response with morphologic CT changes in gastric cancer liver mets similar to those observed in CRC pts with bevacizumab, consistent with antiangiogenic activity. Further analyses in a randomized setting to correlate CT morphologic response with survival are planned. [Table: see text]

Complete Pathologic Response in Advanced Primary Gastric Signet-Ring Cell Carcinoma: A Case Report

Background: Gastric signet ring cell carcinoma (SRC) is a poorly differentiated adenocarcinoma in which the tumour cells invade singly or in small groups. The incidence of SRC has been reported in china as 13.9% (662 patients of 4,759) [1]. It is reported to occur more frequent among women and young patients. A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. Case presentation: A 38-year-old female presented with a 3 weeks history of epigastralgia. Her medical history was unremarkable. The endoscopic findings of the stomach revealed an infiltrative lesion, which the guided biopsy yielded a positive pathologic diagnosis of signet ring cell carcinoma. Diagnostic imaging with an abdominal computed tomography (CT) scan revealed a gastric thickening, with lymph nodes. Induction chemotherapy was recommended, based on 6 cycles of ECX (Epirubicin 50 mg/m2, Cisplatin 60 mg/m2, Capecitabine 625 mg/m2). The total gastrectomy specimen showed a pathological complete response. The patient, who is always followed in consultation, is in complete remission 19 months after the diagnosis Conclusion: SRC is a distinctive histological type of gastric cancer. The ECX or EOX (epirubicin, oxaliplatine, capecitabine) remains the standard treatment of advanced primary gastric signet-ring cell carcinoma. Our case illustrates a complete pathologic response to ECX, which confirmed the effectiveness of this protocol on this histology.

Bevacizumab Falls Short in Treating Advanced Gastric Cancer

The effectiveness of multiagent chemotherapy is limited in advanced gastric cancer: <50% of patients respond to treatment, and survival is usually <1 year. To assess whether adding the antiangiogenic agent bevacizumab to chemotherapy would improve overall survival (OS) in this setting, investigators conducted a multinational, randomized, double-blind, placebo-controlled phase III trial (AVAGAST) involving 774 patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Patients …

Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment

The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400mg/m2 i.v. over two hours followed by 5-FU 400mg/m2 i.v. bolus then 5- FU 2400 mg/m2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. There was no difference between chemonaive and not chemonaive pts treated as firstline in terms of response rate 37% (95% CI: 25-50) vs 44% (95% CI: 21-69), median PFS, 6.7 (95% CI: 5.5-9.9) vs 5.3 months (95% CI: 3.6-6.9) (P = 0.25), and OS, 13.1 (95% CI: 11.7-18.7) vs 8.8 months (95% CI: 7.3—15.6) (P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8-39) vs 22% (95% CI: 6-48), median PFS, four months (95% CI: 2.8-5.4) vs 3.5 months (95% CI: 2.3-4.5) (P = 0.56), and OS, 10.4 months (95% CI: 5.4-14.4) vs 5.3 months (95% CI: 3.5-11.3) (P = 0.58), respectively. The global grade 3-4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.

Hepatic Lipoma: Radiological Imaging Findings

Hemangiomas and hepatic metastases are the leading reasons of echogenic masses on ultrasound (US) evaluation of the liver. Lipomas of the liver are extremely rare and have been sporadically reported in the literature during the last century. The present report describes a patient with hepatic lipoma together with liver metastases from gastric adenocarcinoma. A 54 years old woman was refered to our department because of abdominal pain. Patient has been operated for gastric adenocarcinoma 3 months ago she was evaluated with US, computed tomography (CT) and magnetic resonance imaging (MRI).The abdominal US revealed a 12 × 10 mm echogenic mass with smooth borders in 7th segment of the liver. CT scan showed a hypodense lesion in the same hepatic segment with fat dencity and no contrast involvement. MRI demonstrated the same lesion on T1 and T2 weighted images as hyperintence mass. The final radiographic diagnosis was he-patic lipoma. However, there was metastas in the liver of patient. Patient died 4 months later due to metas-tatic gastric adenocarcinoma. Hepatic lipoma should be kept in mind in echogenic masses on US evaluation of the liver.

Metastatic Gastric Adenocarcinoma Presenting as a Solitary Plaque on the Palm

Cutaneous metastases from gastric adenocarcinoma are extremely rare. When present, metastasis typically signifies disseminated disease with a poor prognosis. We report a case of an 80-year-old male with gastric cancer who presented with a single, erythematous plaque on the left palm, a very rare site for skin metastasis. Results of a skin biopsy demonstrated that the cutaneous metastasis originated from the stomach. This report emphasized the need for appropriate investigation into newly appearing, unusual, or persistent skin lesions.

DNA polymeraseη protein expression predicts treatment response and survival of metastatic gastric adenocarcinoma patients treated with oxaliplatin-based chemotherapy

BackgroundDNA polymerase η (pol η) is capable of bypassing DNA adducts produced by cisplatin or oxaliplatin and is associated with cellular tolerance to platinum. Previous studies showed that defective pol η resulted in enhanced cisplatin or oxaliplatin sensitivity in some cell lines. The purpose of the present study was to investigate the role of pol η protein expression in metastatic gastric adenocarcinoma.MethodsFour gastric adenocarcinoma cell lines were chosen to explore the relationship between pol η protein expression and oxaliplatin sensitivity by western blotting and MTT assay. Eighty metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX regimen as first-line chemotherapy were analyzed, corresponding pretreatment formalin-fixed paraffin-embedded tumor tissues were used to detect pol η protein expression by immunohistochemistry. Relationship between pol η protein expression and clinical features and outcome of these patients was analyzed.ResultsA positive linear relationship between pol η protein expression and 48 h IC50 values of oxaliplatin in four gastric cancer cell lines was observed. Positivity of pol η protein expression was strongly associated with poor treatment response, as well as shorter survival at both univariate (8 versus 14 months; P < 0.001) and multivariate (hazard ratio, 4.555; 95% confidence interval, 2.461-8.429; P < 0.001) analysis in eighty metastatic gastric adenocarcinoma patients.ConclusionsOur study indicates that polη is a predictive factor of treatment response and survival of metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX as first-line chemotherapy. Therefore confirming the value of polη in studies with prospective design is mandatory.

Choroidal metastasis of gastric adenocarcinoma as a first sign of systemic disease recurrence: case report

To describe a patient with unilateral metastatic choroidal gastric adenocarcinoma as a first sign of systemic dissemination. A 54-year-old woman presented with a 7-month history of progressive pain and decrease in vision in her left eye. She had undergone total gastrectomy due to gastric adenocarcinoma two years previously. Examination of the left eye revealed an elevated creamy yellow choroidal tumor infiltrating the macular area and extending around the optic nerve head, suggesting metastasis. Treatment was enucleation of the affected eye. There was orbital recurrence of the tumor, leading to exenteration. Orbital and intraocular metastasis are generally associated with a bad prognosis. This patient represents a rare occurrence of metastatic gastric adenocarcinoma to the choroid, developing as a first sign of systemic recurrence.

Hearing loss as an unusual consequence of metastatic gastric adenocarcinoma.

A sixty-one year old man was referred with a history of progressive dysphagia, vomiting and weight loss with some back pain. Upper gastrointestinal endoscopy and biopsies revealed a gastro-oesophageal junction adenocarcinoma. Despite the absence of metastatic disease on computed tomography, positron emission tomography demonstrated multiple vertebral and sternal deposits. He was reviewed in an ENT clinic with a sudden onset of hearing loss accompanied by dizziness, but no focal neurology. Magnetic resonance imaging identified bilateral 2cm lesions at the internal auditory meatus, consistent with a diagnosis of bilateral acoustic neuromas. The patient subsequently died of carcinomatosis and, because of the potential familial significance of bilateral acoustic neuromas, a limited post-mortem examination was carried out. Unexpectedly, this revealed bilateral adenocarcinoma metastases infiltrating the internal auditory meatus affecting the acoustic nerves. The authors believe this a very rare presentation of metastatic gastric disease.

Microangiopathic hemolytic anemia and leukoerythroblastic blood film heralding bone marrow metastatic gastroesophageal adenocarcinoma

Despite modern technological advancements in laboratory hematology, the blood film remains an important diagnostic aid. Herein, we report the case of a patient with a history of gastric cancer, who presented seven years following apparently successful surgery and adjuvant chemo-radio-therapy, with blood film findings of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and leukoerythroblastosis (LEB). Although mimicking features of thrombotic thrombocytopenic purpura (TTP), subsequent bone marrow examination instead revealed an association with occult recurrence of necrotic, metastatic gastric adenocarcinoma. This case report and literature review highlight these rare, but important, hematological manifestations of gastric cancer, and the importance of astute laboratory and bone marrow investigations in preventing delays in appropriate treatment of the underlying malignancy.

The efficacy and toxicity of modified docetaxel, cisplatin and 5-fluorouracil combination therapy for 27 patients with advanced stage gastric adenocarcinoma

Objective The aim of this study was to evaluate the efficacy and toxicity of modified docetaxel, cisplatin and calcium folinate (CF)/5-fluorouracil (mDCF) combination therapy for 27 patients with recurrent or metastatic gastric adenocarcinoma (R/MGC).

Immune‐mediated pancytopenia induced by oxaliplatin: a case report

Drug-induced immune pancytopenia is considered an uncommon disorder. A 76-year-old woman with metastatic gastric adenocarcinoma received 15 cycles of FOLFOX-6 (oxaliplatin/folinic acid/fluorouracil) with a complete response. Upon disease progression, she was restarted on FOLFOX; during the seventh cycle of treatment, 1 hour after completing her oxaliplatin infusion, she presented oral bleeding, petechiae and generalized hematomas. Her platelet (PLT) count decreased from 164 x 10(9)/L to less than 5 x 10(9)/L within a 3-hour period and her white blood cells (WBCs) decreased from 5 x 10(9) to 1.5 x 10(9)/L. One day later she presented a decrease in hemoglobin level (from 11.4 to 10 g/dL, reaching 8.9 g/dL after 5 days). The patient's PLT and lymphocyte count started to recover after 3 days of immunosuppressive treatment. PLT, red blood cell (RBC), and WBC antibody detection tests were performed in the presence and absence of oxaliplatin. PLT-associated antibodies were evaluated by monoclonal antibody immobilization of PLT antigen assay and flow cytometry; WBC antibodies were tested by flow cytometry; and RBC antibodies were evaluated by gel and indirect antiglobulin test tube testing drug-treated RBCs and untreated RBCs in the presence of drug. Positive reactions were obtained only in the presence of the drug (1 mg/mL) for all tests performed (PLTs, RBCs, and WBCs). Our case convincingly demonstrates that oxaliplatin led to the production of drug-dependent PLT, RBC, and WBC antibodies inducing pancytopenia in the patient. The oxaliplatin was discontinued and patient's hematologic values recovered to normal levels.