Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Realities of KRAS-mutated non-small cell lung cancer

No abstract available.

Pancreatic Metastasis from Invasive Ductal Carcinoma of the Breast / 대한내과학회지

Pancreatic metastases from primary breast cancer are very rare. We report a case of pancreatic metastasis from invasive ductal carcinoma 13 years after the initial diagnosis of breast cancer. When the pancreatic mass was discovered, it was believed to be a primary pancreatic cancer due to the long interval from the initial diagnosis of breast cancer to metastasis. However, it was confirmed as metastatic breast cancer based on the pathology after surgical removal. Follow-up imaging has shown no recurrence.

A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We examined the efficacy of poziotinib, a second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) in patients with lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR-TKIs. MATERIALS AND METHODS: This single-arm phase II study included EGFR-mutant lung adenocarcinoma with AR to erlotinib or gefitinib based on the Jackman criteria. Patients received poziotinib 16 mg orally once daily in a 28-day cycle. The primary endpoint was progression-free survival (PFS). Prestudy tumor biopsies and blood samples were obtained to determine resistance mechanisms. RESULTS: Thirty-nine patients were treated. Tumor genotyping was determined in 37 patients; 19 EGFR T790M mutations and two PIK3CA mutations were detected in the prestudy tumors, and seven T790M mutations were detected in the plasma assay. Three (8%; 95% confidence interval [CI], 2 to 21) and 17 (44%; 95% CI, 28 to 60) patients had partial response and stable disease, respectively. The median PFS and overall survival were 2.7 months (95% CI, 1.8 to 3.7) and 15.0 months (95% CI, 9.5 to not estimable), respectively. A longer PFS was observed for patients without T790M or PIK3CA mutations in tumor or plasma compared to those with these mutations (5.5 months vs. 1.8 months, p=0.003). The most frequent grade 3 adverse events were rash (59%), mucosal inflammation (26%), and stomatitis (18%). Most patients required one (n=15) or two (n=15) dose reductions. CONCLUSION: Low activity of poziotinib was detected in patients with EGFR-mutant non-small cell lung cancer who developed AR to gefitinib or erlotinib, potentially because of severe-toxicityimposed dose limitation.

Anti-Cancer Therapy of Advanced Lung Cancer in Elderly Patients / 대한내과학회지

Lung cancer is not only the most common cancer of the elderly but is also the leading cause of cancer-related mortality in Korea. Therefore, the elderly form a large subgroup of patients with advanced lung cancer. Aging is associated with co-morbidities, poor performance status, and impaired organ function. These problems can cause uncertainty when selecting the optimal treatment for advanced lung cancer, and some elderly patients could be undertreated. Patients with non-squamous histology lung cancer, regardless of age or performance status, should be tested for epidermal growth factor receptor (EGFR) mutations; patients with EGFR mutations such as del 19 or L858R are able to receive EGFR tyrosine kinase inhibitors. The treatment options for elderly patients with lung cancer include best supportive care, single agent chemotherapy, platinum-based doublet chemotherapy, and targeted therapy. The optimum therapeutic option for elderly individuals with advanced lung cancer must be selected carefully, taking into account both the risks and benefits.

Anti-Cancer Therapy of Advanced Lung Cancer in Elderly Patients / 대한내과학회지

Lung cancer is not only the most common cancer of the elderly but is also the leading cause of cancer-related mortality in Korea. Therefore, the elderly form a large subgroup of patients with advanced lung cancer. Aging is associated with co-morbidities, poor performance status, and impaired organ function. These problems can cause uncertainty when selecting the optimal treatment for advanced lung cancer, and some elderly patients could be undertreated. Patients with non-squamous histology lung cancer, regardless of age or performance status, should be tested for epidermal growth factor receptor (EGFR) mutations; patients with EGFR mutations such as del 19 or L858R are able to receive EGFR tyrosine kinase inhibitors. The treatment options for elderly patients with lung cancer include best supportive care, single agent chemotherapy, platinum-based doublet chemotherapy, and targeted therapy. The optimum therapeutic option for elderly individuals with advanced lung cancer must be selected carefully, taking into account both the risks and benefits.

Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. MATERIALS AND METHODS: One hundred twenty cancer patients with pain (numeric rating scale [NRS] > or = 4) and sleep disturbance (NRS > or = 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator\'s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. RESULTS: A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea. CONCLUSION: HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.

Hemothorax caused by spontaneous rupture of a metastatic mediastinal lymph node in hepatocellular carcinoma: a case report

No abstract available.

Arsenic trioxide induces depolymerization of microtubules in an acute promyelocytic leukemia cell line / 대한혈액학회지

BACKGROUND: Arsenic trioxide (As2O3) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As2O3 in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As2O3 activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division. In this study, we investigated how As2O3 induces apoptosis by causing microtubule dysfunction. METHODS: Cultured NB4 cells were treated with As2O3, paclitaxel, and vincristine. Flow cytometric analysis was then performed. An MTT assay was used to determine drug-mediated cytotoxicity. For tubulin polymerization assay, each polymerized or soluble tubulin was measured. Microtubule assembly-disassembly was measured using a tubulin polymerization kit. Cellular microtubules were also observed with fluorescence microscopy. RESULTS: As2O3 treatment disrupted tubulin assembly resulting in dysfunctional microtubules that cause death in APL cells. As2O3 markedly enhanced the amount of depolymerized microtubules. The number of microtubule posttranslational modifications on an individual tubulin decreased with As2O3 concentration. Immunocytochemistry revealed changes in the cellular microtubule network and formation of polymerized microtubules in As2O3-treated cells. CONCLUSION: The microtubules alterations found with As2O3 treatment suggest that As2O3 increases the depolymerized forms of tubulin in cells and that this is potentially due to arsenite's negative effects on spindle dynamics.

The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients

The development of gastric cancer (GC) is closely related to chronic inflammation caused by Helicobacter pylori infection, and herpes virus entry mediator (HVEM) is a receptor expressed on the surface of leukocytes that mediates potent inflammatory responses in animal models. However, the role of HVEM in human GC has not been studied. Previously, we showed that the interaction of HVEM on human leukocytes with its ligand LIGHT induces intracellular calcium mobilization, which results in inflammatory responses including induction of proinflammatory cytokine production and anti-bacterial activities. In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-alpha and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. aureus and production of reactive oxygen species. Our results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of GC.

Clinical significance of PML/RAR alpha isoforms in acute promyelocytic leukemia / 대한내과학회지

BACKGROUND/AIMS: There are three types of PML-RAR alpha mRNA fusion transcripts associated with acute promyelocytic leukemia (APL): the short (S)-form, the long (L)-form and the variable (V)-form. No study on the Korean population has addressed the clinical significance of the specific types of PML-RAR alpha mRNA fusion transcripts for APL patients who receive the combination therapy of all-trans-retinoic-acid and idarubicin (AIDA regimen). METHODS: We performed a retrospective analysis on 94 patients with APL to evaluate differences in the therapeutic outcomes, such as the response rate, an event-free survival (EFS), and overall survival (OS), after remission following the induction of chemotherapy. We also analyzed whether differences in the pretreatment clinical characteristics depend on the PML-RAR alpha isoform. RESULTS: The median age of the patients was 41 years (range 15-85). Among the 94 patients, there were 58 L-form cases (62.1%), 32 S-form cases (34.0%), and 4 V-form cases (4.3%). The CR rate following remission induction treatment was 84.9%. The CR rate was higher in patients with an initial WBC <10.0x109/L, as compared to patients with an initial WBC higher than 10.0X109/L (93.5% vs. 65.4%, p=0.001). The AIDA induction regimen was associated with a better EFS than non-AIDA induction regimens (81.9% vs. 49.6%, p=0.006). The induction group was also a significant prognostic factor for EFS in the multivariate analysis (p=0.020). There were no differences in OS and EFS in patients with either isoform L or isoform S in the AIDA induction group. CONCLUSIONS: This retrospective study demonstrated that pretreatment clinical characteristics and treatment outcomes were not significantly different among patients with varying PML-RAR alpha isoform types in the AIDA induction group.

Anorectal and gastric peripheral T-cell lymphoma, unspecified in a non-AIDS patient

Anorectum is a rare location for malignant lymphoma. Involvement of is rare even for the lymphoma associated with acquired immune deficiency syndrome (AIDS), and AIDS has a relatively increased frequency of anorectal lymphoma. Most lymphomas in AIDS patients are of a B-cell origin, and T-cell lymphoma of the gastrointestinal tract is extremely rare. We report here on a case of anorectal and gastric peripheral T-cell lymphoma, unspecified (PTCLu) in a non-AIDS patient. A previously healthy 29-year-old man presented with hematochezia and tenesmus that he had suffered with for the previous 2 months. Sigmoidoscopy showed anal and rectal submucosal tumor. Multiple round-shaped, flat and elevated lesions were noted on the gastric antrum and body as well. He underwent excisional biopsy for the anal mass and the diagnosis was PTCLu. Biopsies of the gastric lesions gave the same diagnosis. There was no lymphoma involved in the bone marrow. At admission, no antibodies against human immunodeficiency virus were detected. He underwent systemic chemotherapy and upfront autologous stem cell transplantation.

A Case of Pancreatic Cancer Presenting as Dermatomyositis

Dermatomyositis is an idiopathic, inflammatory myopathy characterized by proximal muscle weakness and cutaneous lesions. The association of malignancy with dermatomyositis is well established, especially with lung, breast, ovary, stomach, and colorectal cancers. The incidence of cancer appears to be increased especially in elderly person, and the prognosis is very poor. Malignancy may occur before the onset of dermatomyositis, concurrently, or afterward. Therefore extensive screening tests for an occult malignancy should be conducted in patient with dermatomyositis. We report a 76-year-old man presented with dermatomyositis and a search for possible occult malignancy found an otherwise asymptomatic pancreatic adenocarcinoma with massive lymph node metastasis.

A Less Intensive Combination of Paclitaxel and Carboplatin in Advanced Non-small Cell Lung Cancer Patients who Have Aged 60 Years or More and Has a Poor Performance Status

BACKGROUND: The aim of this study was to evaluate the response, survival, and toxicities of a less intensive combination of paclitaxel and carboplatin, which is used in advanced non-small cell lung cancer (NSCLC) patients older than 60 years of age including those with a poor performance status. METHODS: Thirty patients received 135 mg/m2 of paclitaxel on day 1, and carboplatin was administered to the patients on day 1 every 4 weeks over an area under the concentration-time curve of 6. RESULTS: The response rate was 40%, the median overall survival was 9.1 months (95% CI, 4.2 to 14 months), and the 1 year survival rate was 31%. The median progression-free survival was 7.7 months (95% CI, 3.1 to 12.2 months). In addition, the toxicities were generally mild and reversible. CONCLUSION: This study demonstrates that a less intensive combination of paclitaxel/carboplatin is active and well tolerated in advanced NSCLC patients who are older than 60 years including those with a poor PS 3~4.

Combination Chemotherapy with 5-Fluorouracil and Heptaplatin as First-line Treatment in Patients with Advanced Gastric Cancer

Heptaplatin is a recently developed platinum derivative. This agent has been reported to have a response rate of 17% as a single agent, and tolerable toxicity in the treatment of advanced gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of a combination of 5-fluorouracil (5-FU) and heptaplatin in patients with advanced gastric cancer. Forty-seven chemotherapy-naive patients with advanced or recurred gastric cancer were recruited. 5-FU was administered over 120 hr by continuous intravenous infusion from day 1 to 5, at a daily dose of 1,000 mg/m2 and heptaplatin was administered over 1 hr by intravenous infusion on day 1 at 400 mg/m2, and this cycle was repeated every 4 weeks. The response rate was 21%, median progression-free survival was 1.9 months (95% CI, 1.6 to 2.2 months). Median overall survival was 6.2 months (95% CI, 4 to 8.4 months) and the 1-yr survival rate was 29% for all patients. The most frequent toxicity was proteinuria. Toxicities were generally mild and reversible. This study demonstrates that the combination of 5-FU/heptaplatin combination is less active but tolerated in patients with advance gastric cancer.

A Case of Thrombotic Thrombocytopenic Purpura Achieved Complete Remission with 54 Plasma Exchanges / 대한혈액학회지

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, renal disorder and neurologic signs. Its clinical course is rapid and its mortality rate is very high. However, the prognosis has much improved after plasma exchange was introduced as a therapeutic modality. We report a 31-year-old multipara pregnant woman with refractory TTP, who achieved complete remission after 54 plasma exchanges.

Active Immunization Using Dendritic Cells Mixed With Tumor Cells Inhibits The Growth Of Lymphomas

Dendritic cells (DCs) are potent antigen-presenting cells for the induction and activation of cytotoxic T lymphocytes. We tested whether bone marrow derived DCs are capable of inducing protective immunity against a murine lymphoma (A20). DCs were grown from tumor-bearing BALB/c mice by culturing bone marrow cells. BALB/c mice were injected (sc) with A20 cells on day 0. Intraperitoneal immunization with DCs mixed with lethally irradiated A20 cells were started when the tumor reached ca. 4-5 mm in diameter (Group A) or on day -7 (Group B). Booster immunizations were given every 3-4 days for four weeks. By 31 days in group A, there was a significant reduction in tumor growth in the mice immunized with DCs mixed with irradiated A20 cells as compared with the control groups (p=0.016). In group B, tumor growth was completely inhibited and there was no tumor growth following extended observations after completion of immunization. Thus, DCs mixed with irradiated tumor cells can induce an antitumor effect. This provides a rationale for the use of DCs mixed with irradiated tumor cells in immunotherapy for minimal residual disease of lymphomas.

The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.

A case of bone marrow necrosis due to miliary tuberculosis / 대한내과학회지

Bone marrow necrosis is most frequently diagnosed at postmortem examination. Antemortem diagnosis is uncommon. However, organized studies using either bone marrow biopsy specimens or autopsy material showed that bone marrow necrosis can be demonstrated in approximately one third of specimens. Bone marrow necrosis has been observed during the course of a wide variety of diseases, most commonly in association with acute and chronic leukemia, carcinoma, malignant lymphoma, infections, and sickle cell disease. We report one case of bone marrow necrosis due to miliary tuberculosis. Although appropriate diagnosis and treatment were performed, the patient expired.

Gemcitabine Therapy in Patients with Advanced Pancreatic Cancer

BACKGROUND: Advanced, unresectable pancreatic cancer is an extremely aggressive disease. The 5-year survival rate for pancreatic cancer is only less than 5%. Current therapeutic options for patients with locally advanced or metastatic disease are limited. This analysis is a retrospective evaluation of the efficacy and toxicity of gemcitabine regimen as first-line chemotherapy in patients with advanced pancreatic cancer. METHODS: Seventeen chemotherapy-na ve patients with advanced or recurred pancreatic cancer were consecutively treated. Gemcitabine was diluted in normal saline and administered intravenously over 1 hour. Gemcitabine 1,000 mg/m2 was administered once weekly for 3 out of every 4 weeks. RESULTS: The median age of patients was 55 years (range 44~82 years). Based on RECIST criteria, there were 5 cases of stable disease (45%) and 6 cases of progressive disease (55%) among the 11 assessable patients. The median survival time was 189 days (range, 84 to 409 days), the 1 year survival rate was 18% in all 17 patients. Grade 3~4 toxic side effect was leucopenia only (29%) and was easily managed without infection. CONCLUSION: Gemcitabine is well tolerated, but has no objective response in advanced pancreatic cancer.