NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.

Long-term safety and efficacy of deferasirox in patients with myelodysplastic syndrome, aplastic anemia and other rare anemia in Taiwan.

OBJECTIVE: Patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemia require chronic blood transfusions which can lead to iron overload and subsequent excess iron-mediated complications. Intensive iron chelation with deferasirox could remove excess iron and can alleviate these events; however, the long-term safety and efficacy in Chinese population are not clearly characterized. This study examined the long-term efficacy and safety of deferasirox in a real-world setting in Taiwan. METHODS: This observational, non-interventional, single-arm, multi-center, phase IV study was designed to collect the safety and clinical information about patients who were treated with deferasirox according to investigator's judgment and in accordance with the general clinical practice. RESULTS: From 2009 to 2011, patients with MDS (N = 38), AA (N = 23), and other rare anemias (N = 18) were enrolled. The mean deferasirox exposure was 17.7 ± 4.02 mg/kg/day. The most common drug-related AEs were skin disorders (32.9%) and gastrointestinal disorders (30.4%), while grade 3-4 AEs were rare (5.1%). In the overall patient population, deferasirox effectively decreased serum ferritin levels at 1 year (P = 0.0154) and 3 years (P = 0.0424) from the baseline. Upon the use of deferasirox, 32.9% patients showed erythroid response and 16.7% patients had platelet response. CONCLUSIONS: For patients with MDS, AA, and other rare anemias, the AEs observed in this 3-year surveillance study with deferasirox were mostly mild or moderate. In addition, the hematological response rate was higher than that in the EPIC study, which primarily enrolled Caucasian patients.

Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) of follicular helper T-cell origin and is rare in Taiwan. There are overlapping features of AITL and peripheral T-cell lymphoma with a follicular growth pattern (PTCL-F). Around one fifth of PTCL-F exhibits t(5;9)(q33;q22)/ITK-SYK chromosomal translocation, which is essentially absent in AITL. We retrospectively investigated 35 cases of AITL from Taiwan with histopathology review, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBV) and fluorescence in situ hybridization (FISH) for t(5;9)(q33;q22)/ITK-SYK and correlated the results with overall survival. Twenty-six cases of not otherwise specified PTCL (PTCL-NOS) were also examined by FISH for comparison. Most AITL patients were male (69%) and elderly (median age at 67 years) with frequent bone marrow involvement (53%), high Ann Arbor stages (77%), and elevated serum lactate dehydrogenase (68%). Most cases (80%) showed a typical CD4+/CD8- phenotype and in 90% cases there were scattered EBV-positive B-cells (less than 10% cells). None of these cases showed t(5;9)(q33;q22)/ITK-SYK translocation by FISH. Gain of ITK and SYK gene was identified in 38% and 14% tumors, respectively, but both were not associated with overall survival. Performance status < 2 was associated with a better outcome but not the other clinicopathological factors. All PTCL-NOS cases were negative for ITK-SYK translocation with similar rates (38% and 12%, respectively) of gains at ITK and SYK loci as that of AITL. In this so far the largest series of AITL from Taiwan, we reported the clinicopathological features and FISH findings on ITK and SYK genes. We confirmed the absence of t(5;9)(q33;q22)/ITK-SYK translocation, which may serve as an additional differential diagnostic tool from PTCL-F when present. PTCL-NOS shared a similar pattern of ITK and SYK gains with AITL. More studies are warranted to elucidate the roles of SYK and ITK and other genes in the lymphomagenesis of AITL in Taiwan.

Spectrum of Epstein-Barr virus-associated T-cell lymphoproliferative disorder in adolescents and young adults in Taiwan.

Epstein-Barr Virus (EBV) is a herpesvirus usually infecting B-cells but may occasionally infect T- or natural killer (NK)-cells. EBV-associated T- or NK-cell lymphoproliferations represent a continuous spectrum of diseases ranging from asymptomatic infection, infectious mononucleosis (IM), to clonal and malignant lymphoproliferations including systemic EBV-positive T/NK-cell lymphoproliferative disease (EBV-T/NK-LPD) of childhood and hydroa-vacciniforme-like lymphoma of the skin. The clonal diseases are more prevalent in East Asia and exhibit overlapping clinical and pathological features with chronic active EBV infection. Here we report our experience on 10 cases of EBV-associated T-cell lymphoproliferation from Taiwan including five males and five females with a median age of 18 years old (range, 15-28). The most common clinical symptoms were fever, neck mass and hepatosplenomegaly. Eight of these patients showed elevated lactate dehydrogenase level and half of the patients had cytopenia. All patients had either elevated EBV antibody titers or increased serum EBV DNA levels. Five cases were clinically IM-like with polyclonal (3 cases) or clonal (2 cases) T-cell lymphoproliferation. Two patients each had chronic active EBV infection (CAEBV) and hemophagocytic lymphohistiocytosis (HLH). One patient had both CAEBV and HLH. One of the HLH patients with marrow infiltration by intra-sinusoidal large atypical lymphocytes experienced a fulminant course. In a median follow-up time of 21.5 months, seven patients were free of disease, one was alive with disease, and two died of disease in 31 and 3 months, respectively, despite chemotherapy. We confirmed a wide clinicopathological range of EVB-associated T-cell lymphoproliferation in Taiwan. Furthermore, monomorphic LPD and the single case with fulminant course as defined by Ohshima et al (Pathol Int 2018) as categories A3 and B, respectively, died of disease despite chemotherapy. Our report, the largest series in the recent decade from Taiwan, adds to the understanding of these rare diseases with variable clinical and histopathological presentations.

A postmarketing surveillance study on erbitux (cetuximab) in patients with metastatic colorectal cancer refractory to irinotecan-containing treatment.

OBJECTIVE: This postmarketing surveillance study evaluated the safety and efficacy of cetuximab therapy in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. METHODS: Patients with EGFR-expressing mCRC who had failed prior irinotecan-based chemotherapy and were receiving cetuximab therapy were monitored for treatment efficacy and safety from the time of first infusion until 28 days after the last infusion regardless of the reasons fordiscontinuation. The study followed 269 patients for approximately 2 years. RESULTS: No unexpected adverse events associated with cetuximab therapy were reported, and most events were grade 1 or 2. The most common drug-related adverse events of any grade were rash (21.6%) and dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%), dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for patients receiving second-/third-line (177 patients) or above therapy (92 patients) was associated with a median progression-free survival time of 3.37 and 3.90 months, respectively, and a median overall survival time of 17.6 and 21.1 months, respectively. The response rates for the second-/third-line treatment and fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P = 0.428). CONCLUSION: Cetuximab showed no unexpected safety findings and was efficacious in treating patients with EGFR-expressing mCRC in community practice in Taiwan.

Bcl-6 expression and lactate dehydrogenase level predict prognosis of primary gastric diffuse large B-cell lymphoma.

BACKGROUND/PURPOSE: The gastrointestinal tract is the most common site of primary extranodal non-Hodgkin lymphoma, and the prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) differ in various studies. METHODS: We retrospectively searched for PG-DLBCL in a single institution, performed immunohistochemical analysis, classified tumor phenotype (Hans and Muris algorithms), reviewed medical records, and analyzed the clinical and immunophenotypic variables using Cox proportional hazard regression model. RESULTS: A total of 46 cases were identified including 25 males and 21 females with a median age of 63.5; 18 (39%) were at stage I and 28 (61%) at stage II. Seven (15%) patients underwent surgery as initial treatment including total (n = 3, 7%) and subtotal (n = 4, 9%) gastrectomy. Thirty-three patients (72%) received frontline chemotherapy treatment including ten with additional rituximab (MabThera) injection, and two (6%) of these patients developed perforation after chemotherapy. Four patients passed away shortly after diagnosis and the remaining three were lost to follow-up. The overall 2- and 5- year survival rates were 55% and 50%, respectively. The expression of various differentiation markers was CD10 (25%), bcl-2 (50%), bcl-6 (84%), and MUM1 (64%). Half of the cases studied (22/44) were classified as germinal center B-cell (GCB) phenotype and the remaining half as non-GCB according to Hans algorithm; 66% and 34% cases belonged to groups 1 and 2, respectively, according to Muris algorithm. Univariate analysis showed the expression of bcl-6 by the tumor cells as a favorable factor, while elevated serum lactate dehydrogenase (LDH) level, bcl-2 expression, and Muris group 2 were associated with poorer outcome. Multivariate analysis revealed that the two prognostic factors were bcl-6 expression and elevated LDH level, with hazard ratios of 0.09 (p = 0.002) and 3.72 (p = 0.024), respectively. CONCLUSION: In this retrospective study with heterogeneous treatment modality, we identified bcl-6 expression and elevated LDH level as two prognostic factors for PG-DLBCL.

Thalidomide for the treatment of myelodysplastic syndrome in Taiwan: results of a phase II trial.

BACKGROUND: Thalidomide inhibits angiogenesis and exerts complex immunomodulatory activities. This phase II study aimed to examine the efficacy of thalidomide in Taiwanese patients with myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Sixty patients [intention to treat group (ITT)] with MDS were treated with thalidomide (100 mg/day, increased by 100 mg/day weekly to a maximum of 400 mg/day) for 12 weeks. Forty-two patients of the ITT group were considered as comprising the evaluable population (EP). RESULTS: Thalidomide resulted in hematological improvement (HI) in 28% of ITT analysis and in HI in 40% of the EP. Thalidomide was more effective for MDS patients with low to intermediate-1 International Prognostic Score System scores. The response rates were 7% for ITT and 10% for EP patients. Only two patients exhibited a cytogenetic response. Net reduced levels of vascular endothelial growth factor and basic fibroblast growth factor cytokines were observed in the peripheral blood and the bone marrow of thalidomide-treated patients. CONCLUSION: Low-dose thalidomide is an effective and safe treatment for patients with low-risk MDS.

Therapy-related acute lymphoblastic leukemia with t(4;11)(q21;q23) masqueraded as marrow lymphocytosis in a patient with breast cancer.

Therapy-related acute leukemia develops in patients after chemotherapy and/or radiotherapy for a prior cancer, and most cases are acute myeloid leukemia with a much lower frequency of acute lymphoblastic leukemia (ALL). One unique feature of these therapy-related ALL (t-ALL) is an increased incidence of chromosome band 11q23 aberrations as compared with de novo ALL. In adult female patients, breast cancer is the most common primary cancer. Herein, we report the case of a 49-year-old Taiwanese lady who developed t-ALL with t(4;11)(q21;q23) 16 months after cyclophosphamide, epirubicin, and 5-fluorouracil chemotherapy for her breast cancer. The unusual feature is that the t-ALL was heralded 4 months ago by marrow lymphocytosis comprising atypical small lymphocytes with condensed chromatin mimicking a B-cell chronic lymphoproliferative disorder. Retrospective studies using additional antibodies for immunophenotyping and PCR-based clonality study for immunoglobulin gene rearrangement showed that these atypical small lymphocytes shared similar features with the leukemic blasts at the frank leukemic stage. Our results suggest that these atypical small lymphocytes are lymphoblasts in disguise and that the clinicopathological correlations with ancillary pathological studies are important to reach a definitive diagnosis of such an unusual case.

Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND & AIMS: Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. METHODS: Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. CONCLUSIONS: Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.

Rasch analysis of positive changes following adversity in cancer patients attending community support groups.

OBJECTIVE: This study assessed the 38-item Perceived Benefits Scale (PBS) by examining whether the items constructed a single latent trait and formed an interval scale. This would justify its use to measure the advantages of benefit-finding brought to patients with different cancers from participation in community-based cancer support groups. METHODS: A total of 300 patients were randomly recruited from a 1300-bed medical centre in Taiwan. The Rasch rating scale model was used to examine the model-data fit. Differential item functioning (DIF) analysis was conducted to verify construct equivalence across groups. Comparisons were made among demographic characteristics for various types of patient support groups. RESULTS: Of the 38 items on the PBS, 28 were applicable to cancer patients and were divided into two distinct unidimensional domains; both met the Rasch model's expectation to constitute a single construct. DIF was found between types of cancer patients, but not between genders. Positive changes following adversity were statistically significantly associated with and ascribed to the duration of patient attendance in community-based cancer support groups. CONCLUSION: The two domains verified by Rasch analysis can be used through Rasch-transformed measures to make further statistical inference when comparing positive changes following adversity within and between cancer groups. The psychometric properties of the PBS verified by Rasch modeling fit to the unidimensionality, but need a huge sample size to support its validity and reliability in future studies. Nonetheless, we should be cautious to make comparisons among types of cancer patients due to DIF exhibited in scale.

Upper aerodigestive tract lymphoma in Taiwan.

AIM: To better understand the spectrum of primary lymphomas in the upper aerodigestive tract, a common site of extranodal lymphoma. MATERIALS AND METHODS: Lymphoma cases diagnosed at an institution in southern Taiwan from 1992 to 2007 were retrospectively studied with pathology and history review, immunohistochemistry, in situ hybridisation for Epstein-Barr virus (EBER-ISH), and statistical analysis. RESULTS: 70 patients were identified. The male to female ratio was 2:1, and the median age was 61.5 years (range 8-87); 73% of cases occurred in Waldeyer's ring or the oral cavity. Phenotypically, there were 45 (64%) B cell and 25 (36%) T cell or extranodal natural killer (NK)/T cell lymphoma (ENKL) including 42 (60%) diffuse large B cell lymphomas (DLBCLs), 22 (31%) ENKLs, three unspecified peripheral T cell lymphomas, two follicular lymphomas and one Burkitt lymphoma. EBER-ISH was positive in three (7%) of 42 DLBCLs and all 22 ENKLs. Most patients received chemotherapy with or without radiotherapy. The 5-year overall survival for all patients was 56.3% with B and T or NK/T cell lymphomas at 66.0% and 40.6%, respectively. Univariate analysis revealed that sinonasal presentation, T or NK/T cell phenotype, raised lactate dehydrogenase (LDH) activity, and Ann Arbor stage III/IV diseases were associated with prognostically significant higher hazard ratio (HR) of lymphoma-related death. However, only raised LDH remained significant on multivariate analysis. For DLBCLs, only raised LDH was prognostically significant on either univariate or multivariate analysis. CONCLUSIONS: Only a limited number of lymphoma entities occurred primarily in this anatomical region. The 5-year overall survival rate was comparable to other reports, and raised LDH at diagnosis was the only significant prognostic factor identified. A relatively high incidence of EBV positivity was identified in DLBCLs in this anatomical region, and further studies are warranted to elucidate the clinicopathological significance of these tumours.

Lymphohistiocytic anaplastic large cell lymphoma involving skin: a diagnostic challenge.

Systemic anaplastic large cell lymphoma (ALCL) involving the skin should be differentiated from primary cutaneous CD30-positive T-cell lymphoproliferative disorders. The lymphohistiocytic variant of ALCL (LH-ALCL) is rich in reactive histiocytes with relatively few neoplastic cells, which pose a diagnostic challenge. We present a case of LH-ALCL involving skin mimicking granulomatous inflammation. A 30-year-old woman presented with cervical lymphadenopathy and multiple non-tender, non-itching, erythematous papules over the neck, chest, and abdomen. Biopsy of the cervical lymph node showed LH-ALCL with null cell phenotype. Microscopically, the cutaneous lesion was located predominately around the hair follicle, with numerous reactive histiocytes and scanty medium-sized lymphoma cells expressing CD30 and anaplastic lymphoma kinase (ALK) protein. Furthermore, an ALK gene rearrangement was demonstrated by locus-specific interphase fluorescent in situ hybridization, confirming cutaneous involvement with LH-ALCL. LH-ALCL involving the skin is a rare event, and the numerous reactive histiocytes may mask scanty tumor cells. In addition to B-and T-cell markers, (dermato) pathologists must be aware of this entity in cutaneous lymphohistiocytic proliferations and perform immunostaining for CD30 and ALK to reach a correct diagnosis.

Phase II study of oxaliplatin in combination with continuous infusion of 5-fluorouracil/leucovorin as first-line chemotherapy in patients with advanced gastric cancer.

This study was designed to determine the efficacy and safety of biweekly oxaliplatin in combination with infusional 5-fluouracil (5-FU) and leucovorin in patients with advanced gastric cancer (AGC). Fifty-five eligible patients with measurable or assessable M/AGC (median age 62 and 90% of patients presented with metastasis) received oxaliplatin (85 mg/m2) intravenous infusion for 2 h, followed by intravenous infusion of 5-FU (3000 mg/m2) and leucovorin (100 mg/m2) for 46 h every 14 days until the patient's disease was either in progression, unacceptable toxicity, patient's withdrawal or the investigators' decision to discontinue treatment. Of the 55 enrolled patients, 48 were evaluable for response. Three patients (5.4%) showed complete remission and 20 patients (36.4%) achieved partial response. The overall response rate was 47.9%. Nineteen patients (34.5%) had stable disease and six patients (10.9%) showed progressive disease. The median time to progression was 5.6 months and the median overall survival was 10.8 months. Grade 3/4 toxicities included leucopenia (12.7%), thrombocytopenia (5.4%), diarrhoea (3.6%) and vomiting (9.1%). Peripheral neuropathy was noted in 61.8% of the patients (grade 1/2: 54.5%; grade 3: 7.3%). Our study confirmed that the combination of oxaliplatin and continuous infusion of 5-FU/leucoverin without bolus 5-FU as first-line chemotherapy is active for patients with AGC and relatively safe with lower haematological toxicity.

A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial.

UNLABELLED: Lamivudine is effective to control hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the optimal treatment protocol remains undetermined. In this study, HBV carriers with newly diagnosed non-Hodgkin's lymphoma (NHL) who underwent chemotherapy were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment groups. Group P patients started lamivudine from day 1 of the first course of chemotherapy and continued treatment until 2 months after completion of chemotherapy. Group T patients received chemotherapy alone and started lamivudine treatment only if serum alanine aminotransferase (ALT) levels elevated to greater than 1.5-fold of the upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during the 12 months after starting chemotherapy. During chemotherapy, fewer group P patients had HBV reactivation (11.5% versus 56%, P = 0.001), HBV-related hepatitis (7.7% versus 48%, P = 0.001), or severe hepatitis (ALT more than 10-fold ULN) (0 versus 36%, P < 0.001). No hepatitis-related deaths occurred during protocol treatment. Prophylactic lamivudine use was the only independent predictor of HBV reactivation. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the 2 groups. Two patients, both in group P, died of HBV reactivation-related hepatitis, 173 and 182 days, respectively, after completion of protocol treatment. When compared with an equivalent group of lamivudine-naïve lymphoma patients who underwent chemotherapy, therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation. CONCLUSION: Prophylactic lamivudine use, but not therapeutic use, reduces the incidence and severity of chemotherapy-related HBV reactivation in NHL patients.

Human umbilical cord blood-derived CD34+ cells can be used as a prophylactic agent for experimental heatstroke.

We attempted to assess the prophylactic effect of human umbilical cord blood-derived CD34(+) cells in experimental heatstroke. Anesthetized rats, 1 day before heat stress, were divided into 2 major groups and given CD34(-) cells (defined by 1 x 10(6) human cord blood lymphocytes and monocytes that contained <0.2% CD34(+) cells) or CD34(+) cells (defined by 1 x 10(6) human cord blood lymphocytes and monocytes that contained >95% CD34(+) cells). They were exposed to ambient temperature of 43 degrees C for 70 min to induce heatstroke. When the CD34(-) cells-treated or untreated rats underwent heat stress, their survival time values were found to be 20-24 min. Pretreatment with CD34(+) cells significantly increased survival time (123-351 min). As compared with normothermic controls, all CD34(-) cells-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, these heatstroke reactions all were significantly suppressed by CD34(+) cells pretreatment. In addition, the levels of interleukin-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34(+) cell administration during heatstroke. Our data indicate that human umbilical cord-derived CD34(+) cells can be used as a prophylactic agent for experimental heatstroke.

A phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline.

PURPOSE: The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy. METHODS: This phase-I study was performed via a two-staged dose escalation schema. The initial doses were PLD 30 mg/m2 and PTX 150 mg/m2, administered intravenously once every 21 days. The dose of PLD was escalated in increments of 5 mg/m2 until the MTD was reached, at which time the PTX was then increased in increments of 10 mg/m2 until the MTD was reached. RESULTS: Twenty-three patients received between 1 and 13 treatment cycles. In stage I of the study, 14 patients received a fixed dose of PTX 150 mg/m2 while PLD escalated from 30 mg/m2. At 40 mg/m2, PLD resulted in dose-limiting toxicities (DLT) including febrile neutropenia and palmar-plantar erythrodysesthesia that occurred in two of five patients. In stage II of the study, nine patients received fixed dose of PLD 35 mg/m2 and escalating doses of PTX starting at 160 mg/m2. At PTX 170 mg/m2 and dose-limiting neutropenic fever occurred in two of five patients. Out of 19 evaluable patients, 10 (52.6%) achieved objective response (one complete response and nine partial response), and 5 had stable disease. CONCLUSIONS: The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m2, respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m2) and PTX (150-160 mg/m2) constitutes an active regimen with mild toxicity that merits further study.

p53 and p27 as predictors of clinical outcome for rectal-cancer patients receiving neoadjuvant therapy.

Our aim was to examine whether certain molecular markers, specifically p53, p21, p27, and Bcl-2, could be used to predict the tumor response of rectal cancer to neoadjuvant therapy and determine the overall and disease-free survival rates of patients following neoadjuvant therapy. Seventy-seven patients with rectal cancers were used in this study. All of them received neoadjuvant therapy and 53 of them were given radical surgery. Immunohistochemical tests were performed for the four markers mentioned above using biopsy specimens obtained from 70 of the patients prior to radiation. The identical tests were performed for the same markers using excised specimens from the patients after radical surgery. For the pre-radiation specimens, the positive rate for having p27 and Bcl-2 markers was 32.7% and 16.6%, respectively. This rate increased to 73.5% and 41.6% (p=0.001 and 0.012, respectively) in the specimens obtained after the surgery. With respect to "fair response (FR)" of patients, the pre-radiation biopsy specimens showed significant difference for the p53 (-) and p27 (+) markers (p=0.006). Patients with a 3-year overall survival rate were found to have, from their surgical specimens, 92% of the p27 (+) and 75% of p27 (-) markers (p=0.0058). Our study showed: first, the rate of positive identification of molecular markers, p27 and Bcl-2, increased following neoadjuvant therapy. Second, either the p53 (-) or p27 (+) status was a good predictor for FR in the pre-radiation biopsy specimens. Third, patients with p27 (+) markers in the surgical specimens lived longer at 3 years.

T-cell and NK/T-cell lymphomas in southern Taiwan: a study of 72 cases in a single institute.

In an attempt to better understand the clinicopathologic features of T- and natural killer (NK)/T-cell lymphomas in Taiwan and the distribution and relative frequency of each subtype according to the new WHO classification, the pathology file of a medical center in southern Taiwan during 1989-2002 was retrospectively searched. The results of light microscopy, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBER), and T-cell receptor (TCR)-gamma chain gene rearrangement were correlated with clinical findings. A total of 72 cases were identified. They were peripheral T-cell lymphoma, unspecified (PTLu; n = 23, 31.9%), NK/T-cell lymphoma (n = 14, 19.4%), anaplastic large cell lymphoma (n = 13, 18.0%), angioimmunoblastic T-cell lymphoma (AITL; n = 9, 12.5%), precursor T-lymphoblastic lymphoma (n = 8, 11.1%), enteropathy-type intestinal T-cell lymphoma (n = 2, 2.8%), adult T-cell leukemia/lymphoma (n = 2, 2.8%), and subcutaneous panniculitis-like T-cell lymphoma (n = 1, 1.4%). The male to female ratio was 1.5:1. Forty patients (55.6%) had extranodal presentation. Eleven cases including 9 of 14 (64.3%) NK/T-cell lymphomas expressed CD56. All 14 NK/T-cell lymphomas are EBER-positive. Seven of nine (77.8%) AITLs expressed CD10. The overall 5-year survival rate was 10.2%. In conclusion, we have characterized a large series of T- and NK/T-cell lymphomas in southern Taiwan, where there is male predominance and poor prognosis. CD56 is a specific but not very sensitive marker while EBER is most reliable for the diagnosis of NK/T-cell lymphoma. CD10 is a useful marker to differentiate AITL from PTLu.

Anaplastic large cell lymphoma--a rare disorder in southern Taiwan.

Anaplastic large cell lymphoma (ALCL) is a subgroup of non-Hodgkin's lymphomas with large lymphoma cells expressing CD30 antigen. This entity has rarely been reported in Taiwan. We performed a retrospective clinicopathologic study in a medical center in southern Taiwan during a 13-year period and identified 13 cases. There were 10 males and 3 females with a median age of 49 years old. Seven presented with pure nodal disease and 5 had bony involvement. The staging results were stage I (5 patients), II (1), III (1), and IV (4). The pathologic subtypes were common variant (10), lymphohistiocytic variant (2), and small cell variant (1). Eleven tumors were of T-cell lineage; 2, null-cell. Immunohistochemically, 5 tumors (38.5%) expressed cytotoxic markers, T-cell intracellular antigen-1 and/or granzyme B. Two tumors (15.4%) expressed anaplastic lymphoma kinase (ALK). Long-term follow-up information was available in 8 patients. The 2 patients with ALK-expressing tumors (37 and 49 years old) were free of disease for 61 and 54 months, respectively. The other 6 patients were either died of disease (5 patients) or experienced relapse with progressive disease (1). In conclusion, we reported the largest series of ALCL in Taiwan. We confirmed ALK-expressing ALCL carries favorable prognosis and ALK-negative ALCL has similar poor prognosis as non-anaplastic T-cell lymphoma. As compared to the previous reports from the West, our ALK positive rate was lower and the age of our ALK-positive patients was older. A larger national or multi-institutional study is needed for further characterization of ALCL in Taiwan.