Ta Chung Chao

N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data

Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3–4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85xa0mg/m2) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200xa0mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2–4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2–4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Rituximab therapy increased post-transplant cytomegalovirus complications in Non-Hodgkin’s lymphoma patients receiving autologous hematopoietic stem cell transplantation

The use of monoclonal antibody, rituximab, had been reported to be associated with some severe viral infections. The inference of rituximab therapy and post-transplant cytomegalovirus (CMV) infectious complications in non-Hodgkin’s lymphoma (NHL) patients is still unclear now. From 2002 to 2005, 46 patients with relapsed indolent or high-risk aggressive B cell NHL who received rituximab (17 patients) or not (29 patients) before autologous hematological stem cell transplantation (HSCT) in one institute were retrospectively analyzed for the risk factors of CMV complications after transplantation. Pre-transplant and post-transplant CMV infectious conditions, conditioning regimens, transplant types, and post-transplant complications were recorded. Post-transplant infectious complications were followed up until 6xa0months after transplantation.Seventeen of 46 patients received rituximab before HSCT. Three of them suffered from CMV infection and two of them developed CMV disease. All of the patients with CMV disease recovered after ganciclovir and CMV-specific immunoglobulin therapy. Twenty-nine of 46 patients without rituximab treatment before HSCT did not have CMV complications after HSCT. The risks to develop CMV infections after autologous HSCT were higher in rituximab-treated patients (17.6% vs 0%, pu2009=u20090.045, Fisher exact test, two-sided). The risks to develop CMV diseases had higher trend with rituximab therapy than without rituximab therapy (11.7% vs 0%, pu2009=u20090.131, Fisher exact test, two-sided). The NHL patients receiving rituximab therapy had higher risk to develop CMV infectious complications after autologous HSCT.

Higher fungal infection rate in elderly patients (more than 80 years old) suffering from diffuse large B cell lymphoma and treated with rituximab plus CHOP

Although adding rituximab to standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy is an efficacious and well-tolerated regimen in elderly patients with diffuse large B cell lymphoma (DLBCL), it may increase susceptibility to opportunistic infections, and such cases have been reported. Our study was to identify the risk factors for fungal infection in a retrospective case-control matched study of 34 elderly DLBCL patients treated with rituximab plus CHOP (R-CHOP) and 35 control patients treated with the standard CHOP regimen at the Taipei Veterans General Hospital, Taiwan. The rate of overall infection was similar in both groups. However, subgroup analysis found that the fungal infection rate was significantly different, 41.7 and 17.1%, in the R-CHOP and CHOP groups, respectively, (Pu2009=u20090.03). Univariate analysis identified the rituximab plus CHOP chemotherapy regimen (Pu2009=u20090.03), age older than 80xa0years (Pu2009=u20090.04), and bone marrow involvement (Pu2009=u20090.04) as risk factors for development of fungal infection, whereas, multivariate regression analysis identified only rituximab plus CHOP and old age. Adding rituximab to the standard CHOP regimen in elderly DLBCL patients might increase the incidence of fungal infection especially in those older than 80xa0years old.

Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma

We aimed to study the prevalence and prognostic influence of epidermal growth factor receptor (EGFR) and its downstream effectors in synovial sarcoma (SS).

Biweekly oxaliplatin plus 1-day infusional fluorouracil/leucovorin followed by metronomic chemotherapy with tegafur/uracil in pretreated metastatic colorectal cancer

PurposeMetronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (UFT) was incorporated into an oxaliplation/infusioanl fluouracil (5-FU)/leucovorin (LV) protocol in this study. The primary endpoints were response rate, time to progression (TTP) and safety profile in 5-FU-pretreated metastatic colorectal cancers (CRCs).Patients and methodsTwenty-eight patients with metastatic CRCs resistant or refractory to 5-FU/LV were enrolled. Chemotherapy was administrated every 2xa0weeks sequentially with 2-h infusion of oxaliplatin (85xa0mg/m2) and LV (200xa0mg/m2), intravenous bolus 5-FU (400xa0mg/m2), 22-h infusion of 5-FU (600xa0mg/m2) on day 1 and then followed by 10-day daily oral UFT (200xa0mg/m2)/LV (30xa0mg/m2).ResultsPartial response was seen in ten (35.7%) patients. The median TTP was 5.2 (95% CI: 4.16–6.31) months and the median overall survival was 13.4 (95% CI: 6.39–20.5) months. No grade 3 toxicities above 5% according to National Cancer Institute-Common Toxicity Criteria (NCI-CTC) occurred except sensory neuropathy (10.7%). No grade 4 toxicity, treatment-related mortality or hand–foot syndrome was found.ConclusionsThis study protocol with favorable toxicity profile is thus promisingly effective against 5-FU-pretreated metastatic CRCs. Given the present experience, an evaluation of the regimen as front-line treatment of metastatic CRC is planned.

High prevalence of SV40 infection in patients with nodal non-Hodgkin's lymphoma but not acute leukemia independent of contaminated polio vaccines in Taiwan

Recent studies have linked simian virus 40 (SV40) to non-Hodgkins lymphoma (NHL), especially in countries in which people were exposed to contaminated polio vaccines prior to 1963. In Taiwan, nearly all children were not exposed to contaminated polio vaccine during this period; the relationship between SV40 infection and hematological malignancies is unclear and deserves to be studied. Using PCR amplification of SV40 large T antigen DNA, confirmed by Southern blot hybridization and sequence analysis, 91 frozen lymph nodes from NHL patients were examined. Thirteen (14.3 percent) showed positive for SV40. All other test samples, including diagnostic bone marrow from patients with acute leukemia, peripheral blood from 10 relatives of SV40 positive-patients and 91 age-matched normal volunteers, and 5 reactive hyperplastic lymphoid tissues, showed negative. These results may reflect that human-to-human transmission of SV40 is independent of contaminated polio vaccines; and SV40 is possibly associated with the development of NHL in Taiwan (p = 0.0001). Prospective studies are needed to determine the prevalence of SV40 infections in our and other human populations and to explore the means of transmission of the virus.

Sudden-Onset Pancytopenia with Intracranial Hemorrhage after Oxaliplatin Treatment: A Case Report and Literature Review

Oxaliplatin is a third-generation platinum compound and has been widely employed in the treatment of colorectal cancer. Despite its good efficacy, it is reported to induce immune-mediated cytopenia. We report the case of a 78-year-old male patient who experienced acute pancytopenia along with coagulopathy and intracranial hemorrhage after his 17th course of oxaliplatin. This condition appeared immediately after completion of oxaliplatin infusion, and was persistent despite aggressive transfusion and treatment with granulocyte colony-stimulating factor. The patient died 72 h after the administration of oxaliplatin. The only preceding symptom was chills 30 min after initiation of oxaliplatin, although steroid was given as premedication. We review the literature describing oxaliplatin-induced cytopenia, and discuss the manifestation, immune mechanism and treatment of this condition. We conclude that any symptoms that occur during infusion of oxaliplatin should not be overlooked but should be taken seriously as they may represent a little spark that kindles a great fire, and that steroids may provide an effective treatment for oxaliplatin-induced cytopenia. However, a major complication in our patient may still happen. Further studies for the mechanism and the predictive markers of oxaliplatin-induced cytopenia are worthy.

Sequential therapy with capecitabine followed by vinorelbine/cisplatin in patients with anthracycline/taxane-refractory metastatic breast cancer

Background: Currently, there is no standard treatment for patients with anthracycline and taxane‐refractory metastatic breast cancer (MBC). Capecitabine or vinorelbine plus cisplatin is an effective palliative regimen for taxane‐refractory MBC. In this study, we analyzed the efficacy and toxicity of sequential therapy with capecitabine followed by biweekly vinorelbine plus cisplatin in 37 patients with anthracycline and taxane‐refractory MBC in Taipei Veterans General Hospital. Methods: Capecitabine (2,500 mg/m2 twice daily for 2 weeks, followed by 1 week of rest) was repeated every 3 weeks until the disease progressed. Patients then received biweekly vinorelbine (25 mg/m2) plus cisplatin (40 mg/m2) (arm A, n = 17) or best supportive care (BSC) (arm B, n = 20) in accordance with patient preference and clinical judgment. The clinical variables and response to capecitabine were well balanced in both arms. Results: The overall response rate to capecitabine was 32%, with a complete response rate of 5% and a partial response rate of 27%. Stable disease was achieved in an additional 46%. The disease control rate with capecitabine was 78%. Median progression‐free survival and overall survival with capecitabine were 5.9 and 9.5 months, respectively. There was a trend toward better overall survival in arm A patients compared with arm B (BSC) patients, though statistical significance was not reached (10.4 vs. 7.4 months; p = 0.08); however, a significantly better overall survival rate was observed in the subgroup with capecitabine‐controlled disease (10.8 vs. 6.9 months; p = 0.015). The safety profile of vinorelbine/cisplatin was acceptable: only 6% developed grade 4 neutropenia. Conclusion: We suggest that sequential therapy is not necessarily effective compared with capecitabine alone, but is probably effective in patients initially controllable with capecitabine.

Relatively favorable outcomes of post-transplant pulmonary function in patients with chronic myeloid leukemia receiving non-myeloablative allogeneic hematopoietic stem cell transplantation.

Abstract:u2002 Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen‐matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post‐transplant function from January 1995 to December 2002. Of 20 patients, eight received non‐myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12u2003months post‐transplant. Possible pre‐HSCT and post‐HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non‐myeloablative conditioning therapy. We conclude that non‐myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post‐transplant pulmonary function changes.

Role of PLK1 signaling pathway genes in gastrointestinal stromal tumors

In previous studies by the authors, aurora kinase A (AURKA) was demonstrated as an independent poor prognostic marker for the recurrence of localized gastrointestinal stromal tumors (GISTs) and for the progression of advanced GISTs. In the present study, the prognostic effect of genes involved in cell cycle regulation in GISTs was further examined. Leading edge analysis in gene set enrichment analysis was used to identify the most common genes in the top 10 enriched gene sets of high-risk patients with GISTs in a Japanese study. The obtained gene list was uploaded to the Pathway Interaction Database to search for critical pathways. Selected genes within the pathway were subsequently verified through immunohistochemistry (IHC) in another cohort of patients. A total of 5 genes in ‘PLK1 signaling events,’ namely AURKA, polo-like kinase 1 (PLK1), cell division cycle 25C (CDC25C), budding uninhibited by benzimidazoles (BUB1), and targeting protein for Xklp2 (TPX2), were identified for subsequent study. Among the Japanese cohort, all 5 genes, except BUB1, were significant prognostic factors for poor recurrence-free survival (RFS). Among 141 patients enrolled for the IHC study, all 5 genes exhibited variable expression patterns. In the association study, only AURKA exhibited significant overexpression in non-gastric tumors. Although all 5 genes were considered as risk factors for poor RFS based on a univariate analysis, only the mitotic count and expression levels of CDC25C, BUB1, and TPX2 retained prognostic effects in the multivariate analysis. The PLK1 signaling pathway is crucial in the disease progression of GISTs. Genes within this pathway may serve as predictive markers for adjuvant therapy.