Secondary hematological malignancies in patients with sarcoma: A single­center retrospective study.

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

Chromosome aberration dynamics in breast cancer patients treated with radiotherapy: Implications for radiation biodosimetry.

Although radiological accidents often result in partial-body radiation exposure, most biodosimetry studies focus on estimating whole-body exposure doses. We have evaluated time-dependent changes in chromosomal aberrations before, during, and after localized fractionated radiotherapy. Twelve patients with carcinoma in situ of the breast who underwent identical adjuvant radiation therapy (50 Gy in 25 fractions) were included in the study. Lymphocytes were collected from patients before, during, and after radiotherapy, to measure chromosome aberrations, such as dicentric chromosomes and translocations. Chromosome aberrations were then used to calculate whole- and partial-body biological absorbed doses of radiation. Dicentric chromosome frequencies in all study participants increased during radiotherapy (p < 0.05 in Kruskal-Wallis test). Increases of translocation frequencies during radiotherapy were observed in seven of the twelve patients. The increased levels of dicentric chromosomes and translocations persisted throughout our 1-year follow-up, and evidence of partial-body exposure (such as Papworth's U-value > 1.96) was observed more than 1 year after radiotherapy. We found that cytogenetic biomarkers reflected partial-body fractionated radiation exposure more than 1 year post-exposure. Our findings suggest that chromosome aberrations can be used to estimate biological absorbed radiation doses and can inform medical intervention for individuals suspected of fractionated or partial-body radiation exposure.

Association of EGFR mutations in second primary lung cancer and HER2 expression in breast cancer survivors.

BACKGROUND: The incidence of second primary lung cancer (SPLC) is increasing with longer survival rates from breast cancer. Despite of studies to suggest the mutual exclusivity of epidermal growth factor receptor (EGFR) and human epidermal growth receptor 2 (HER2) in several cancers, the effect of HER2 expression in breast cancer on EGFR mutations in SPLC is unclear. Therefore, this study aimed to determine the association between HER2 expression and EGFR mutations. METHODS: We conducted a retrospective cohort study of breast cancer survivors diagnosed with SPLC after breast cancer treatment between 1997 and 2018. We investigated the association between HER2 expression in breast cancer and EGFR mutations in SPLC, specifically focusing on negative correlations by using logistic regression analysis. RESULTS: EGFR mutations in SPLC were detected in 19 of 38 patients. Analysis for HER2 revealed a statistically significant difference in the proportion of EGFR mutations between patients with SPLC and previous HER2 positive breast cancer (43.5%) and those with SPLC and previous HER2 negative breast cancer (90.0%; P=0.021). The ratio of EGFR mutations decreased with the degree of HER2 expression in patients with previous breast cancer (90.0%: for no HER2 expression, 62.5% for HER2 1+, 0.0% for HER2 2+, and 41.7% for HER2 3+; P=0.018). Multivariate logistic analyses revealed that EGFR mutations in SPLC were significantly associated with age [odds ratio (OR): 1.11, 95% confidence interval (CI): 1.01-0.23, P=0.039] and HER2 positive status (OR: 0.04, 95% CI: 0.01-0.56, P=0.017). CONCLUSIONS: This study suggests that the frequency of EGFR mutations in SPLC may be associated with low HER2 expression in previous breast cancer.

Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial).

BACKGROUND: In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and more convenient to administer than cisplatin. PATIENTS AND METHODS: This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m2/day on days 1-14; oxaliplatin 130 mg/m2 on day 1; every 3 weeks) or SP (S-1 80 mg/m2/day on days 1-14; cisplatin 60 mg/m2 on day 1; every 3 weeks [SP3]). RESULTS: Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS [median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67-1.07]. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66-1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX. CONCLUSIONS: SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01671449.

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study.

BACKGROUND: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods. RESULTS: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. CONCLUSION: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer.

OBJECTIVES: More than half of cases of gastric cancer (GC) are diagnosed in elderly patients (≥70years). While doublet combination with fluoropyrimidines and platinum is currently considered standard first-line chemotherapy in advanced GC, the main goal of chemotherapy remains palliation. MATERIALS AND METHODS: In a multi-center phase III trial, patients with chemotherapy-naïve, metastatic GC, aged 70years or older were randomized 1:1 to receive X monotherapy (capecitabine 1000mg/m2 bid po on days one to fourteen) or XELOX (X plus oxaliplatin 110mg/m2 iv on D1). Treatment was repeated every 21days until disease progression, unacceptable toxicity, or withdrawal. Primary endpoint was overall survival (OS). RESULTS: In total, 50 patients with a median age of 77 (range, 70 to 84) were enrolled (X, n=26; XELOX, n=24). No treatment-related serious adverse events or unexpected toxicities were observed. The most frequently observed toxicities were nausea and hand-foot syndrome, with fatigue and peripheral neuropathy more common in XELOX than in X patients. Median OS was 11.1months for XELOX arm and 6.3months for X arm (HR 0.58, 95% CI 0.30-1.12, P=0.108). Although the difference was not significant, on the basis of evidence of superiority of XELOX seen in the first interim analysis, an independent data monitoring committee recommended early stopping of the trial. PFS was significantly longer (HR 0.32, 95% CI 0.17-0.61, P<0.001) with XELOX (7.1months) than with X (2.6months). CONCLUSION: Platinum-based combination chemotherapy was associated with survival benefit, as compared with X monotherapy in elderly patients with GC.

A phase II trial of modified FOLFOX6 as first-line therapy for adenocarcinoma of an unknown primary site.

PURPOSE: The aim of the study was to assess the clinical activity and toxicity of oxaliplatin and leucovorin in combination with bolus and continuous infusional 5-fluorouracil administered every 2 weeks (modified FOLFOX-6 regimen) to patients with adenocarcinoma of an unknown primary site (ACUP). METHODS: Previously untreated ACUP patients were treated with oxaliplatin (100 mg/m(2)) and leucovorin (200 mg/m(2)) as a 2-h infusion followed by bolus administration of 5-fluorouracil (400 mg/m(2)) and continuous infusion of 5-fluorouracil (2400 mg/m(2)) every 2 weeks. RESULTS: A total of 23 patients were enrolled and treated with a modified FOLFOX-6 regimen between May 2009 and November 2014. This trial was terminated before the scheduled enrollment due to poor accrual. A total of 134 cycles of mFOLFOX-6 were administered to 23 patients. The median number of cycles of mFOLFOX-6 was 5 (range 1-12). Among 20 patients whose tumor responses were evaluable, seven patients showed a partial response (no complete response), with an objective response rate of 35.0%. The median duration of response was 3.9 months (range 3.0-19.8). The median progression-free survival and overall survival were 3.0 and 9.5 months, respectively (95% confidence interval 1.4-6.7 months and 4.8-26.4 months, respectively). Treatment-related toxicity was manageable. CONCLUSIONS: mFOLFOX-6 showed modest activity in treatment-naïve patients with ACUP. A future, prospective large-scale study incorporating a parallel molecular prediction marker study is warranted.

Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP.

The potential role of visceral adipose tissue (VAT) as a prognostic factor in patients with diffuse large B cell lymphoma (DLBCL) treated with frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy was explored. Total adipose tissue and VAT were measured by analyzing positron emission tomography (PET)/computed tomography (CT) images obtained during the initial staging of patients with DLBCL. The VAT ratio was calculated as follows: VAT ratio = VAT area/total adipose tissue area. Body mass index (BMI), sex, and International Prognostic Index (IPI) were also incorporated as co-variates in the final model of multivariate Cox regression analysis for survival. A total of 156 patients with DLBCL, who were treated with frontline R-CHOP, were enrolled in our study. The median patient age was 61 years, and 81 patients were male (51.9 %). The median cycle of R-CHOP was six. The IPI risk group was a strong prognostic factor for progression-free survival (PFS) and overall survival (OS) (p < 0.001). Obese BMIs were an independent prognostic factor for PFS, but not for OS in multivariate analyses, compared to patients with normal BMIs (HR = 0.43, 95 % CI = 0.19-0.98, and p = 0.046 for PFS). A high VAT ratio (third tertile) was an independent adverse prognostic factor for PFS and OS in multivariate analyses (HR = 2.87 and 2.66, 95 % CI = 1.30-6.32 and 1.30-5.44, and p = 0.009 and 0.007 for PFS and OS, respectively). VAT ratio was an independent prognostic factor for patients with DLBCL treated with first-line R-CHOP; thus, additional large prospective studies are warranted.

Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer.

PURPOSE: We conducted a phase II trial of 5-fluorouracil and oxaliplatin combination chemotherapy as a second-line treatment in unresectable/metastatic biliary tract cancer patients who had failed gemcitabine-based chemotherapy. METHODS: Patients treated with gemcitabine-based palliative treatment were enrolled in this study. Patients were received modified FOLFOX3 (mFOLFOX3) consists of oxaliplatin 85 mg/m(2) (day 1) and leucovorin 30 mg (days 1, 2) followed by 5-fluorouracil 1,500 mg/m(2) (days 1, 2) every 2 weeks. RESULTS: Between March 2010 and June 2012, a total of 30 patients were enrolled in this study. Twenty-eight patients were measurable for treatment response. One achieved complete response, and one a partial response was observed. Overall response rate was 7.1% (95% confidence interval 0.9-23.5%). The median progression-free survival was 1.6 months, and the median overall survival was 4.4 months. Grade 3-4 hematologic toxicities included neutropenia (6.7%) and thrombocytopenia (3.4%). The most common non-hematologic toxicity was neuropathy (22.2%). However, the most common grade 3-4 non-hematologic toxicity was hyperbilirubinemia (5.0%). There was one treatment-related death due to neutropenic infection. CONCLUSION: mFOLFOX3 as a second-line regimen has modest effect and tolerable toxicity in unresectable/metastatic biliary tract cancer patients who have been treated previously via gemcitabine-based chemotherapy.

Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study.

PURPOSE: We aimed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin to capecitabine-cisplatin (XP) in patients with previously untreated advanced gastric cancer (AGC). METHODS: In this double-blind, placebo-controlled, phase III study, we enrolled patients aged 18 years or older with histological or cytological confirmed metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ) at nine centres in Korea. Patients, stratified by disease measurability and participating site, were randomly assigned (1:1) to receive capecitabine 1000mg/m(2) twice daily for 14 days and cisplatin 80 mg/m(2) on day 1 every 3 weeks plus either simvastatin 40 mg or placebo, once daily. Cisplatin was given for 8 cycles; capecitabine and simvastatin were administered until disease progression or unacceptable toxicities. This study is registered with ClinicalTrials.gov, number NCT01099085. RESULTS: Between February 2009 and November 2012, 244 patients were enrolled and assigned to treatment groups (120 simvastatin, 124 placebo). Median progression free survival (PFS) for 120 patients allocated XP plus simvastatin was 5.2 months (95% confidence interval (CI) 4.3-6.1) compared with 4.63 months (95% CI 3.5-5.7) for 124 patients who were allocated to XP plus placebo (hazard ratio 0.930, 95% CI 0.684-1.264; p=0.642). 63 (52.5%) of 120 patients in simvastatin group and 70 (56.4%) of 124 had grade 3 or higher adverse events. CONCLUSIONS: Addition of 40 mg simvastatin to XP does not increase PFS in our trial, although it does not increase toxicity. Low dose of simvastatin (40 mg) to chemotherapy is not recommended in untargeted population with AGC.

Clinical characteristics and outcomes of primary bone lymphoma in Korea.

BACKGROUND: This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL). METHODS: We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed. RESULTS: The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions. CONCLUSION: Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.

Cytogenetic biodosimetry for Fukushima travelers after the nuclear power plant accident: no evidence of enhanced yield of dicentrics.

Individuals who traveled to contaminated areas after the Fukushima nuclear accident have concerns about the health effects. However, medical follow-up for any adverse health effects will be difficult without personal dose measurements. Cytogenetic biodosimetry is a reasonable method of assessing absorbed doses retrospectively. We analyzed dicentric chromosomes for 265 Fukushima travelers, mostly journalists and rescue workers, who had been dispatched to northeastern Japan during the nuclear emergency. As a control group, 37 healthy volunteers who had not visited Japan since the accident were enrolled. Yields of dicentrics and absorbed doses calculated from a dose-response calibration curve for travelers and the control group were compared. The cut-off level for dicentric chromosomes in the controls was 3.5 per 1000 cells. Of the 265 travelers, 31 had elevated numbers of dicentrics (High-Dics group) while 234 were below the cut-off (Normal-Dics group). All but one of the individuals in the High-Dics group also reported a significantly higher number of medical exposures to radiation within the past three years compared with the Normal-Dics or control groups. The 225 travelers with no history of medical exposure showed no difference of dicentrics yield compared to the control group. Our data indicate that Fukushima travel alone did not enhance the yield of dicentrics.

A phase II trial of paclitaxel, 5-fluorouracil (5-FU) and cisplatin in patients with metastatic or recurrent gastric cancer.

PURPOSE: We wanted to assess the effectiveness and safety of combination chemotherapy with paclitaxel, 5-fluorouracil (5-FU) and cisplatin for treating advanced gastric cancer. MATERIALS AND METHODS: Patients with metastatic or recurrent gastric cancer were entered into this study. Paclitaxel at a dose of 135 mg/m(2) on day 1, 5-FU 1 g/m(2)/day in a 24 hour continuous infusion from day 1 to day 4 and cisplatin 60 mg/m(2) on day 1 were administered. This regimen was repeated every 3 weeks. RESULTS: A total of 34 patients were enrolled in this study. Among them, 33 patients were finally evaluable for their response. 17 (51.5%) patients had a partial response (95% CI: 26.0 approximately 77.0%). The median duration of overall survival was 13.2 months. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15.2% and 1.1% of all the cycles, respectively. Grade 3 stomatitis and neurotoxicity were observed in 20.6% and 1.1% of all patients, respectively. Grade 4 non-hematologic toxicity was not observed. CONCLUSIONS: The regimen of paclitaxel, 5-FU and cisplatin demonstrated activity and acceptable toxicity for treating metastatic gastric cancer.

Gemcitabine and carboplatin combination chemotherapy for elderly patients with advanced Non-Small Cell Lung Cancer: a feasibility study.

PURPOSE: Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients. MATERIALS AND METHODS: THE ELIGIBILITY CRITERIA WERE AS FOLLOWS: pathologically confirmed NSCLC, an age >or=65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m(2) was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration. RESULTS: From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. The median patient age was 68 years (range: 65 approximately 75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4 approximately 64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy. CONCLUSIONS: Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.

A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma.

PURPOSE: The combination of 5-fluorouracil (5-FU) and cisplatin (FP) remains the mostly used regimen for metastatic esophageal squamous carcinoma. This phase II study assessed the efficacy and safety of capecitabine/cisplatin (XP) as a first-line chemotherapy in a homogenous cohort of patients with metastatic or recurrent esophageal squamous cell carcinoma. MATERIALS AND METHODS: Patients received 60 mg/m(2) of cisplatin intravenously (IV) on day 1 and capecitabine 1,250 mg/m(2)/dose orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until the documented disease progression, unacceptable toxicity, or patient's refusal. Immunohistochemical studies against thymidylate synthase (TS) and thymidine phosphorylase (TP) were performed to seek predictive markers for treatment response. RESULTS: Between December 2003 and March 2006, 45 patients entered the study. All patients had histologically proven squamous cell carcinoma of the esophagus. The overall response rate (ORR) was 57.8% (95% CI, 43.3-72.2) with 0 CR and 26 PRs. The median duration of response in responders was 4.6 months (1.0-15.6 months). With a median follow-up duration of 25.7 months (10.8-42.6 months), the median time to progression was 4.7 months (95% CI, 2.5-7.0) and the median survival time was 11.2 months (95% CI, 8.5-13.9). Common grade 3 or 4 non-hematological adverse events were anorexia (18/191, 9.4%), fatigue (9/191, 4.7%), constipation (6/191, 3.1%), hand-foot syndrome (6/191, 3.1%) and diarrhea (4/191, 2.1%). The most common grade 3 or 4 hematological adverse events were neutropenia (33/191, 17.3%), followed by leucopenia (11/191, 5.8%), anemia (2/191, 1.0%) and thrombocytopenia (1/191, 0.5%). There was no treatment-related death. Neither TS nor TP showed predictive value for treatment response. CONCLUSION: The XP regimen demonstrated a promising antitumor activity in metastatic esophageal squamous cell carcinoma, which may potentially replace the FP regimen.

Postremission therapy for acute myeloid leukemia in the first remission.

The medical records of 99 patients with acute myeloid leukemia (AML; except AML, M3) in the first remission from 1995 to 2004 were retrospectively reviewed. When they achieved complete remission, at first complete remission (CR1), patients received allogeneic (n = 23), autologous hematopoietic stem cell transplantation (HSCT) (n = 35), or intensive chemotherapy (n = 41) according to prognostic factors and donor availability. There was an advantage in terms of event-free survival (EFS, p = 0.0001) and overall survival (OS, p = 0.0002) with HSCT as compared to those of intensive chemotherapy. However, the EFS and OS were not different between allogeneic HSCT and autologous HSCT. In high-risk patients, the EFS and OS of allogenic or autologous HSCT group were higher compared with those in the intensive chemotherapy group (p < 0.01). However, there was no difference between allogeneic HSCT and autologous HSCT in terms of EFS and OS. In the intermediate- or low-risk group, there was no significant difference in the outcome according to the postremission modalities.

A phase II trial of gemcitabine plus capecitabine for patients with advanced pancreatic adenocarcinoma.

PURPOSE: While gemcitabine (GEM) is widely accepted for the treatment of advanced pancreatic cancer, capecitabine (CAP) has shown single agent activity and promising efficacy in combination with GEM. This phase II study was conducted to evaluate the efficacy and toxicity of GEM combined with dose escalated 14-day CAP as first-line chemotherapy for advanced pancreatic cancer. In addition, we also analyzed the correlation between CA19-9 response and clinical outcomes. METHODS: Patients had advanced pancreatic adenocarcinoma, no prior systemic chemotherapy other than that given concurrently with radiation therapy, at lease one measurable disease, and adequate organ functions. The patients were treated with GEM 1,000 mg/m2 IV on days 1, 8 and CAP 1,000 mg/m2 twice a day PO on days 1-14, in 21-day cycles. RESULTS: The objective RR among 45 patients was 40.0% (95% CI; 25.1-54.9), including 1CR (2.2%). The median TTP and OS were 5.4 months (95% CI; 1.8-9.0) and 10.4 months (95% CI; 6.2-14.5), respectively. Patients with >or=25% decline of serum CA19-9 had significantly better outcomes in terms of TTP and OS than those who did not (P < 0.03). The most frequent, grade 3-4, non-hematologic toxicity was hand-foot syndrome (6.7%). CONCLUSIONS: The combination of GEM with dose escalated 14-day CAP is well tolerated and offers encouraging activity in the treatment of advanced pancreatic cancer. In addition, CA19-9 response correlates well with clinical outcomes in this population.