Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients.
This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model.
Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m2 (range, 85 to 1,583 mg/m2). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ≥55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN.
We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.
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This study aims to investigate the current situation of national colorectal cancer screening by analyzing participation rates, positive rates of screening methods and screening rate of secondary screening tests in colorectal screening of the national cancer screening program in 2008.
With database about target population and screened individuals of the national cancer screening program, the results of target population and participants of colorectal cancer screening in 2008 were analyzed. Among adults aged over 50 years of medical aid and beneficiaries of national health insurance paying lower 50% premiums in the total subscribers, 4,640,365 were target population of colorectal cancer screening and the data of 984,915 undergoing fecal occult blood test (FOBT) as a primary screening were analyzed.
The colorectal cancer screening rate was 21.2% and the rates of national health insurance subscribers, females and the elderly aged 60-64 years were higher than those of others. The recipients with a positive result in FOBT recorded approximately 7.5%. Medical aid beneficiaries (7.9%), males (8.8%) and seniors aged over 75 years (9.1%) showed higher positive rates than the average one. Out of the FOBT positive recipients, 43.0% took a secondary screening and the rate undergoing colonoscopy (31.4%) was higher than that of doing double-contrast barium enema test (11.6%).
Colorectal cancer screening rate of medical aid beneficiaries and people paying lower 50% premiums among national health insurance subscribers, was different according to demographic characters (gender, age and types of health insurance). This finding meant that screening for the vulnerable needed to be encouraged by considering socio-demographic characters. Additionally, more efforts were necessary to increase the secondary screening rate of people with a positive result in primary one.
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Korea started breast cancer screening as part of the National Cancer Screening Program (NCSP) in 1999. In order to identify under-served groups, we investigated mammography uptake in the National Breast Cancer Screening Program.
The study population was participants in the National Breast Cancer Screening Program from 2004 to 2008. We analyzed participation rates by insurance type, age group, and area of residence.
Total participation rates for breast cancer screening increased from 18.2% in 2004 to 35.0% in 2008. The participation rate in the group aged 60 to 69 years showed the greatest increase, 21.3%, among the four age groups. Although the screening rate increased continuously, the participation rate of the Medical Aid Program (MAP) group was low compared to the National Health Insurance (NHI) group. Moreover, the increasing trend of mammography uptake in the MAP group was much lower than that of the NHI group.
The participation rate for breast cancer screening in the NCSP in Korea has increased. However, the participation rate in mammography among MAP recipients is still lower than that of NHI beneficiaries. To increase mammography uptake, it is important to make it available to everyone by ensuring inclusion of all population subgroups.
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Systemic chemotherapy is the only option for patients with unresectable/metastatic hepatocellular carcinoma (HCC) who are not candidates for local/regional treatment. However, the response to such treatment and survival are poor, especially in hepatitis B virus (HBV) endemic areas. The aim of this study was to determine the efficacy of cisplatin-based combination chemotherapy and identify a subgroup of advanced HCC patients with favorable responses.
The medical records of all consecutive patients with unresectable/metastatic HCC who received cisplatin-based combination chemotherapy between January 2003 and October 2009 were reviewed. Time to progression (TTP) and overall survival (OS) were determined using Kaplan-Meier analysis. Univariate and multivariate analyses were performed to identify prognostic factors for TTP and OS.
Data for 46 patients were analyzed. First-line chemotherapies consisted of cisplatin-based combination treatment with doxorubicin, fluoropyrimidines and gemcitabine. The response rate for all patients was 4.3%. The median TTP and OS were 1.8 (95%confidence interval [CI], 1.1 to 2.5) and 7.2 (95% CI, 3.0 to 11.5) months, respectively. Eastern Cooperative Oncology Group (ECOG) performance status (PS), Child classification, Cancer of the Liver Italian Program (CLIP) score and portal vein thrombosis (PVT) were identified by univariate analyses as prognostic factors for TTP and OS. ECOG PS (hazard ratio [HR], 4.51; 95% CI, 1.61 to 12.6; p=0.004) and PVT (HR, 2.12; 95% CI, 1.10 to 4.11; p=0.026) were independent prognostic factors for TTP.
Cisplatin-based combination chemotherapy in patients with advanced HCC has a low response rate and short TTP regardless of the chemotherapy regimen used. Patients with a good ECOG PS and without PVT can be considered candidates for cisplatin-based combination chemotherapy.
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We evaluated clinical outcomes after drainage for malignant pericardial effusion with imminent or overt tamponade.
Between August 2001 and June 2007, 100 patients underwent pericardiocentesis for malignant pericardial effusion. Adequate follow-up information on the recurrence of pericardial effusion and survival status was available for 98 patients.
Recurrence of effusion occurred in 30 patients (31%), all of whom were diagnosed with adenocarcinoma. Multivariate analysis indicated that adenocarcinoma of the lung (hazard ratio [HR], 6.6; 95% confidence interval [CI], 1.9 to 22.3; p=0.003) and progressive disease despite chemotherapy (HR, 4.3; 95% CI, 1.6 to 12.0; p=0.005) were independent predictors of recurrence. Survival rates three months after pericardiocentesis differed significantly with the type of primary cancer; the rates were 73%, 18%, 90% and 30% in patients with adenocarcinoma of the lung, squamous cell carcinoma of the lung, breast cancer and other cancers, respectively.
Recurrence and survival of patients with malignant pericardial effusion are dependent on the type of primary cancer and response to chemotherapy. Patients with adenocarcinoma of the lung may be good candidates for surgical drainage to avoid repeated pericardiocentesis, but pericardiocentesis is considered effective as palliative management in patients with other cancers.
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We investigated the clinicopathologic information of patients with gastric cancer with multiple primary cancers (GC-MPC) of three or more sites.
Between 1995 and 2009, 105,908 patients were diagnosed with malignancy at Severance Hospital, Yonsei University Health System. Of these, 113 (0.1%) patients with MPC of three or more sites were registered, and 41 (36.3%) of these were GC-MPC. We retrospectively reviewed the clinical data and overall survival using the medical records of these 41 GC-MPC patients. We defined synchronous cancers as those occurring within 6 months of the first primary cancer, while metachronous cancers were defined as those occurring more than 6 months later.
Patients with metachronous GC-MPC were more likely to be female (p=0.003) and young than patients with synchronous GC-MPC (p=0.013). The most common cancer sites for metachronous GC-MPC patients were the colorectum, thyroid, lung, kidney and breast, while those for synchronous GC-MPC were the head and neck, esophagus, lung, and kidney. Metachronous GC-MPC demonstrated significantly better overall survival than synchronous GC-MPC, with median overall survival durations of 4.7 and 14.8 years, respectively, and 10-year overall survival rates of 48.2% and 80.7%, respectively (p<0.001).
Multiplicity of primary malignancies itself does not seem to indicate a poor prognosis. The early detection of additional primary malignancies will enable proper management with curative intent.
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AMD3100, an antagonist of the CXCR4 chemokine receptor is soon to be used clinically for the peripheral mobilization of hematopoietic stem cells (HSCs) in patients with multiple myeloma. AMD3100 has been shown to activate a G protein coupled with CXCR4 and thus acts as a partial CXCR4 agonist
The effects of AMD3100 on survival and proliferation of two myeloma cell lines (RPMI8226 and U266) as well as CD138+ cells obtained from several patients with multiple myeloma were analyzed by flow cytometry using annexin V and a colorimetric cell proliferation assay (CCK-8 assay).
AMD3100, but not T140, another CXCR4 antagonist, stimulated the proliferation of myeloma cell lines and CD138+ primary human myeloma cells (-2-fold increase) in a dose-dependent manner in serum-free culture for up to 5 days, which was inhibited by pretreating the cells with pertussis toxin. AMD3100 enhanced the proliferation of U266 cells induced by interleukin-6 and partially reversed AG490-mediated growth inhibition and apoptosis induced by serum deprivation in RPMI8226 cells. AMD3100 induced the phosphorylation of Akt and MAPK p44/p42 in U266 cells and MAPK p44/p42 in RPMI8226 cells. In contrast, AMD3100 markedly increased the cell apoptosis and reduced the number of RPMI8226 cells after 5 to 7 days of culture under serum-free conditions.
AMD3100 exerts dual effects, initially enhancing and subsequently inhibiting the survival and proliferation of myeloma cells, signaling
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Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare form of primary liver cancer composed of cells with histopathologic features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of its low incidence, the information on clinical outcomes of cHCC-CC is very limited and there are no published reports describing non-surgical treatment options for cHCC-CC. We report a case of cHCC-CC exhibiting a favorable response to systemic chemotherapy with doxorubicin and cisplatin. A 62-year-old man who recurred after a right lobectomy for cHCC-CC received sorafenib for palliative systemic therapy, but follow up imaging studies showed disease progression. He received 2nd line chemotherapy with doxorubicin at 60 mg/m2 together with cisplatin at 70 mg/m2. After 2 cycles of chemotherapy, a computed tomography scan of the chest showed markedly decreased size and number of the multiple lung metastases. After completing 8 cycles of 2nd line therapy, we changed the regimen to a fluorouracil (5-FU) mono therapy because of the toxicities associated with doxorubicin and cisplatin. To date, the patient has completed his 15th cycle of 5-FU mono therapy with the disease status remaining stable during 18 months of follow-up.
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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease. The prognosis is poor in most cases with rapid progression despite administering chemotherapy. A 67-year-old man complained of skin rashes on his back and this spread to the trunk, face, arms and thighs, and he was initially diagnosed with cutaneous lupus erythematosus according to the skin biopsy. The skin rashes then became aggravated on a trial of low dose methylprednisolone for 3 months. Repeated skin biopsy revealed a diffuse infiltration of lymphoid cells with medium sized nuclei, positive for CD4 and CD56, negative for Epstein-Barr virus (EBV), indicating a diagnosis of BPDCN. Further workups confirmed stage IVA BPDCN involving the skin, multiple lymph nodes, the peripheral blood and the bone marrow. He was treated with six cycles of combination chemotherapy consisting of ifosphamide, methotrexate, etoposide, prednisolone and L-asparaginase, and he achieved a partial response. Herein we report on a rare case of BPDCN that was initially misinterpreted as cutaneous lupus erythematosus.
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The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation.
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