Keon Woo Park

Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma

ObjectiveThe outcome of systemic chemotherapy in metastatic hepatocellular carcinoma (HCC) patients had been disappointing. Based on the demonstrated antitumor activities and different mechanisms of action and toxicity profiles, we designed a phase II trial of combination therapy with doxorubicin and cisplatin in metastatic HCC patients anticipating a synergistic interaction of the combination.MethodsFrom January 1998 to January 2003, 42 consecutive patients with metastatic HCC were accrued. The regimen consisted of doxorubicin 60xa0mg/m2 delivered as an intravenous infusion over 30xa0min on dayxa01, followed by cisplatin 60xa0mg/m2 infused over 1xa0h on dayxa01. The cycle was repeated every 28xa0days. The objective tumor response was evaluated after two or three courses of chemotherapy. The serum alpha-fetoprotein level was measured at the start of every cycle.ResultsIn total, 122 cycles of the regimen were administered, with a median of three cycles per patient (range one to eight cycles). The median age of the patients was 45xa0years (range 19–61xa0years), and 37 were evaluable for treatment response. The objective response rate was 18.9% (95% CI 8.0–35%) with one complete response and six partial responses. Six patients (16.2%) had stable disease and 24 patients (64.9%) had progression. Median overall survival of 37 patients was 7.3xa0months (95% CI 5.9–8.6xa0months). The median time to progression of all evaluable patients was 6.6xa0months (95% CI 5.4–7.8xa0months). Of 37 evaluable patients, 12 32.4%, 95% CI 18.0–49.8%) showed more than 50% decrease in AFP level from their baseline AFP and the median time to decrease in AFP by more than 50% was 1.8xa0months with a range of 0.7–4.7xa0months. The chemotherapy was well tolerated and the most common grade 3/4 side effects were neutropenia (14.3%), thrombocytopenia (11.9%), and diarrhea (9.5%).ConclusionCombination chemotherapy with doxorubicin and cisplatin in metastatic HCC patients showed modest antitumor activity with relatively tolerable adverse effects. The objective response rate of the regimen was comparable to those found in other phase II trials, but the search for the optimal chemotherapy should be continued.

Mitomycin-C and capecitabine as third-line chemotherapy in patients with advanced colorectal cancer: a phase II study.

PurposeThe aim of this study was to investigate the therapeutic value and safety of third-line treatment with mitomycin-C (MMC) and capecitabine (Xeloda) in patients with advanced colorectal cancer pretreated with combination regimens including 5-fluorouracil (5-FU), folinic acid (FA) and irinotecan (CPT-11) or 5-FU, FA and oxaliplatin (L-OHP).Patients and methodsA total of 21 patients (M/F 16/5, median age 60.0xa0years) with advanced colorectal cancer, all of whom had developed progressive disease while receiving or within 6xa0months of discontinuing two sequential chemotherapy lines with 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP, were accrued to this study. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous MMC 7xa0mg/m2 on therapeutic dayxa01 plus oral capecitabine 1000xa0mg/m2 twice daily on daysxa01–14, was initiated. After rest for 7xa0days, capecitabine 1000xa0mg/m2 twice daily was administered on daysxa022–35 followed by 7xa0days rest. Treatment courses were repeated every 6xa0weeks unless there was evidence of progressive disease, unacceptable toxicity or patient refusal of treatment.ResultsAll the patients were assessable for toxicity and 19 for response. The median number cycles of chemotherapy was two (range one to four). Only 1 patient (4.8%) had a partial response, 4 patients (19.0%) had stable disease, and 14 patients (66.7%) progressed. The median follow-up period was 7.3xa0months and median time to progression was 2.6xa0months. The median overall survival was 6.8xa0months. No toxic deaths occurred. Toxicities of third-line treatment were mild and manageable. As NCI/NIH common toxicity criteria, grade 3/4 anemia, neutropenia and thrombocytopenia occurred in two, one and one patients, respectively.ConclusionOur findings suggest that the combination of MMC and capecitabine in patients with advanced colorectal cancer pretreated with combination regimens including 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP is safe. However, this regimen had a poor response rate and no definitive contribution to increasing patients’ overall survival time. Further evaluation of other salvage regimens seems to be warranted.

Dacarbazine-based chemotherapy as first-line treatment in noncutaneous metastatic melanoma: multicenter, retrospective analysis in Asia.

Malignant melanoma, a neoplastic disorder produced by malignant transformation of the melanocyte, is considered to be resistant to chemotherapy. Dacarbazine is one of the standard chemotherapeutic agents in Korea. This study is designed to analyze treatment outcome and delineate prognostic factors based on clinical parameters for patients with advanced malignant melanoma who had received dacarbazine-based chemotherapy. This is a multicenter, retrospective analysis of 95 patients with metastatic malignant melanoma who had received dacarbazine-based chemotherapy, from January 1997 to June 2010. After a median follow-up duration of 41 months (range, 2–191 months), median survival time from the start of treatment was 12.1 months [95% confidence interval (CI): 10.9–13.5]. The overall response rate was 26.3% (95% CI: 17.8–36.4). On univariate analysis, primary site [mucosa of head and neck, gastrointestinal (GI)/genitourinary tract > cutaneous+acral melanoma], metastases to liver, GI tract, and elevated lactate dehydrogenase adversely influenced on survival. At a multivariate level, independent poor prognostic factors were mucosal melanoma [P=0.001; hazard ratio (HR): 2.988; 95% CI: 1.534–5.821], metastasis to GI tract [P=0.040; HR: 2.108; 95% CI: 1.036–4.288], and elevated lactate dehydrogenase (P=0.047; HR: 1.695; 95% CI: 1.007–2.854). Dacarbazine-based chemotherapy seems to be a reasonable option in Asia where mucosal melanoma is more prevalent than in the West. The dacarbazine-based chemotherapy showed an overall response rate of 26.3% and an overall survival of 12.1 months without a significant difference in response rates between noncutaneous or cutnaeous melanoma.

Clinical features and treatment outcomes of angioimmunoblastic T-cell lymphoma

The objective of this retrospective study was to investigate clinical features and treatment outcomes in patients with angioimmunoblastic T-cell lymphoma (AITL), data of which were collected over a 15-year period. Sixty-five patients diognosed with AITL were included in the study. About half of the patients (46.2%) presented with poor performance status (ECOG ≥2); 72.3% of patients belonged to high intermediate or high-risk of IPI and same proportion belonged to Class 2 of PIT (Prognostic index for PTCL-U), and most patients (95.4%) were diagnosed at an advanced stage. At diagnosis, 27 patients (41.5%) presented with malignant pleural effusion, and 22 patients (33.8%) had skin involvment. Most of the initial chemotherapy regimes were anthracycline-based (88.2%). Overall response rate to initial chemotherapy was 86.2% (64.7% of complete response, 21.5% of partial response). The median progression-free survival and overall survival of all patients was 7.1 months (95% CI, 2.8-11.4) and 15.1 months (95% CI, 6.7-23.5), respectively. Age, performance status, and PIT scores were predictive prognostic factors for survival. In conclusion, although AITLs showed a good response to the initial chemotherapy, thier response durations wer short; therefore, chemotherapy for AITL should be modified or intensified as in high-dose chemotherapy.

CHOP followed by involved field radiotherapy for localized primary gastric diffuse large B-cell lymphoma: Results of a multi center phase II study and quality of life evaluation

We aimed to define the role of cyclophosphamide, vincristine, doxorubicin, prednisone (CHOP) followed by involved field radiotherapy (IFRT) for treating localized primary gastric diffuse large B-cell lymphoma (DLBCL). Newly diagnosed patients with localized primary gastric DLBCL were to receive four cycles of CHOP followed by IFRT of 40.0 Gy. At 1 year after the completion of treatment, patients filled out the EORTC Quality of Life Questionnaire specified for stomach cancer (QLQ-C30-STO22). Fifty evaluable patients (25 men, 25 women) were included. The median age was 54.5 years (range, 21 – 73 years. The overall response rate to the CHOP was 94% (95% confidence interval [CI], 87 – 100) in the intent-to-treat population. Forty-one of the 50 patients (82%; 95% CI, 71 – 93) achieved complete remission (CR). After the completion of radiotherapy, five patients who were in PR following chemotherapy eventually attained CR. The overall complete response rate was thus 92% (95% confidence interval, 84 – 99). With a median follow-up period of 30 months, the 2-year progression-free and overall survival rate was 92% and 92%, respectively. The gastric function was well preserved with negligible stomach-related symptoms at 1 year after the completion of treatment. This organ-preserving combined treatment is highly effective and well tolerated for the patients with localized gastric DLBCL.

Retrospective analysis of extra-gastrointestinal stromal tumors.

AIMnTo investigate the clinicopathologic features of patients with extra-gastrointestinal stromal tumors (EGISTs) in South Korea.nnnMETHODSnA total of 51 patients with an EGIST were identified. The clinicopathologic features, including sex, age, location, tumor size, histology, mitotic rate, immunohistochemical features, genetic status and survival data, were analyzed.nnnRESULTSnThe median age was 55 years (range: 29-80 years), and male:female ratio was 1:1.04. The most common site was in the mesentery (n = 15) followed by the retroperitoneum (n = 13) and omentum (n = 8). The median tumor size was 9.0 cm (range: 2.6-30.0 cm) and the median mitotic rate was 5.0/50HPF. (1/50 - 185/50). KIT was analyzed in 16, which revealed 10 cases with wild-type KIT and 6 cases with an exon 11 mutation. Among 51 patients, 31 patients had undergone surgery, and 10 had unresectable disease and had taken palliative imatinib, which resulted in 22.7 mo of progression-free survival. Of the patients who had undergone surgery, 18 did not take adjuvant imatinib, and 8 of these were categorized as high risk according to the risk criteria. However, the relapse-free survival was not different (P = 0.157) between two groups.nnnCONCLUSIONnBecause the biologic behaviors of GISTs differ according to the location of the tumor, a more stratified strategy is required for managing EGISTs including incorporation of molecular features.

IMVP-16/Pd followed by high-dose chemotherapy and autologous stem cell transplantation as a salvage therapy for refractory or relapsed peripheral T-cell lymphomas

The present study aimed to analyse the treatment outcome of IMVP-16/Pd (ifosfamide, methotrexate, etoposide and prednisone) followed by high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with peripheral T-cell lymphomas (PTCLs) who were previously treated with CHOP. Since 1995, 32 PTCL patients were treated with IMPV-16/Pd. Nine of 32 patients achieved a response (5 demonstrating complete response (CR) and 4 partial response), with an overall response rate of 28.1% (95% onfidence interval 0.12–0.45). Considering histopathologic subtypes, 3 of 4 relapsed natural killer (NK)/T-cell lymphoma patients (75%) achieved CR, but only 1 of 6 in non-NK/T-cell lymphoma patients (16.7%) achieved CR (P = 0.19). Six of 9 IMVP-16/Pd sensitive patients underwent HDC/ASCT. Three of them relapsed after 3, 4 and 15 months, respectively, of HDC/ASCT. Estimated 3-year overall survival and progression-free survival rates were 14.2% and 12.2%, respectively. Multivariate analysis revealed that responsiveness to first-line CHOP was a significant prognostic factor (P < 0.05). These results indicate that IMVP-16/Pd followed by HDC/ASCT appears to be an effective salvage regimen, especially for NK/T-cell lymphoma.

Influential Factors for the Collection of Peripheral Blood Stem Cells and Engraftment in Acute Myeloid Leukemia Patients in First Complete Remission

Although several studies have investigated factors influencing peripheral blood stem cell (PBSC) mobilization in patients with nonmyeloid malignancies in an effort to increase the efficiency of autologous PBSC transplantation (APBSCT), there are very few reports on the efficiency of PBSC mobilization in patients with leukemia. We analyzed the effects of influential variables on successful mobilization and the correlation between infused cell doses and engraftment in acute myeloid leukemia (AML) patients in first complete remission (CR1) who received APBSCT. Between May 1998 and May 2003, 34 patients with AML underwent APBSC collections at our institution. All patients were in CR1 at the time of transplantation. Except for 1 patient, all patients successfully achieved the target CD34+ cell yield of ≥2 × 106/kg. Among progenitor cells, the CD34+ cell dose and the colony-forming unit-granulocyte-macrophage count showed significant correlations with neutrophil and platelet engraftments. The time to neutrophil engraftment was inversely correlated to the number of infused CD34+ cells (r = -0.67; P <.001), whereas the time to neutrophil engraftment was not significantly correlated with the number of monocytes (r = 0.20; P =.701) or the number of nucleated cells (r = 0.35; P =.062). The time to platelet engraftment was significantly correlated with the dose of infused CD34+ cells (r = -0.47; P =.012). The univariate analysis showed that more CD34+ cells per kilogram and more CD34+ cells per kilogram per day were collected from patients who had a shorter interval (less than 2 months) between diagnosis and PBSC harvest (P =.0111). In conclusion, this study showed that the CD34+ cell dose was most strongly correlated with a successful engraftment in AML CR1 patients who underwent APBSCT. The proper timing of PBSC collections should be explored to optimize the outcome of APBSCT in AML CR1 patients.

Quality of life one year after chemoradiotherapy for localized primary gastric diffuse large B-cell lymphoma.

We assessed the quality of life (QOL) at least one year after sequential chemoradiotherapy for the treatment of localized gastric diffuse large B-cell lymphoma (DLBCL). We used the EORTC Quality of Life Questionnaire for Stomach Cancer (EORTC QLQ-STO22). Among the 45 patients available at the one-year follow-up after radiation therapy, 40 patients completed the EORTC QLQ-STO22 questionnaire. Their median age was 54.5 (range, 20–70xa0years). Social functioning was most adversely affected among the respondents with a score of 59, whereas other functions and the global scales were preserved above a score of 70 by linearly transformed values. Fatigue, the financial impact and specific emotional problems such as “thinking about their illness” (STO-ANX) and “worry about weight loss or future health” (STO-BI) were persistently bothersome for some patients. Other stomach-related symptoms such as dysphagia, pain, or reflux were negligible at 1xa0year after treatment. Therefore, this organ-preserving combined approach was effective for the maintenance of the QOL and minimization of stomach abnormalities in patients with gastric lymphoma.

Weekly docetaxel and gemcitabine in previously treated metastatic esophageal squamous cell carcinoma

AIMnTo assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate (FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma (SCC).nnnMETHODSnA multi-center, open-label, prospective phase II study was designed. Thirty-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m(2) and gemcitabine 1000 mg/m(2) iv at a FDR (10 mg/m(2) per minute) on days 1 and 8. Treatment was repeated every twenty-one days until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was response rate (RR), and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).nnnRESULTSnCombination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia (97%), fatigue (64%) and neutropenia (55%). One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely excluded. Disease control (objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30% (95%CI: 15%-46%). The median PFS and OS were 4.0 (95%CI: 3.4-4.6) and 8.8 mo (95%CI: 7.8-9.8 mo), respectively.nnnCONCLUSIONnA combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.