Soon Il Lee

Salvage Chemotherapy for Pretreated Gastric Cancer: A Randomized Phase III Trial Comparing Chemotherapy Plus Best Supportive Care With Best Supportive Care Alone

PURPOSE When designing this trial, there was no evidence that salvage chemotherapy (SLC) in advanced gastric cancer (AGC) resulted in substantial prolongation of survival when compared with best supportive care (BSC). However, SLC is often offered to pretreated patients with AGC for anecdotal reasons. PATIENTS AND METHODS Patients with AGC with one or two prior chemotherapy regimens involving both fluoropyrimidines and platinum and with an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned in a ratio of 2:1 to SLC plus BSC or BSC alone. Choice of SLC-either docetaxel 60 mg/m(2) every 3 weeks or irinotecan 150 mg/m(2) every 2 weeks-was left to the discretion of investigators. Primary end point was overall survival (OS). RESULTS Median OS was 5.3 months among 133 patients in the SLC arm and 3.8 months among 69 patients in the BSC arm (hazard ratio, 0.657; 95% CI, 0.485 to 0.891; one-sided P = .007). OS benefit for SLC was consistent in most of the prospectively defined subgroups, including age, PS, number of prior treatments, metastatic sites, hemoglobin levels, and response to prior chemotherapy. SLC was generally well tolerated, and adverse events were similar in the SLC and BSC arms. We found no median OS difference between docetaxel and irinotecan (5.2 v 6.5 months; P = .116). CONCLUSION To our knowledge, this is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.

Gefitinib (ZD1839) Monotherapy as a Salvage Regimen for Previously Treated Advanced Non-Small Cell Lung Cancer

Purpose: A worldwide compassionate-use program has enabled >42,000 patients with advanced non-small cell lung cancer (NSCLC) to receive gefitinib treatment. Here we report the outcome of gefitinib therapy in patients who enrolled in the “Iressa” Expanded Access Program at the Samsung Medical Center. Experimental Design: Patients with advanced or metastatic NSCLC who had progressed after prior systemic chemotherapy and for whom no other treatment option was available were eligible to receive gefitinib treatment as part of the Expanded Access Program. A post hoc assessment of potential prognostic factors for response and survival was performed by multivariate analysis. Results: All 111 evaluable patients had stage IV disease; most patients had a baseline performance status of 2 [n = 52 (47%)] or 3 [n = 18 (16%)] and had received ≥2 prior chemotherapy regimens (56%). The objective response rate was 26%, the disease control rate (measured over ≥8 weeks) was 40%, and the 1-year survival rate was 44%. Adenocarcinoma histology was associated with better response and disease control rates, and a performance status of 0–2 was also associated with a better disease control rate. Both of these factors, as well as female gender, were significantly associated with longer survival. Gefitinib was well tolerated; the most common adverse event was grade 1 skin rash. Conclusions: Gefitinib demonstrated significant antitumor activity and a favorable tolerability profile in this series of NSCLC patients with poor prognosis.

Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: Surgical resection followed by chemotherapy versus chemotherapy alone

The aim of this retrospective cohort study was to analyze the impact of surgery on the outcomes and qualities of life (QOL) in patients with intestinal diffuse large B-cell lymphoma (DLBCL). We assessed 345 patients with either localized or disseminated intestinal DLBCL and compared them according to treatment: surgical resection followed by chemotherapy versus chemotherapy alone. In patients with localized disease (Lugano stage I/II), surgery plus chemotherapy yielded a lower relapse rate (15.3%) than did chemotherapy alone (36.8%, P < .001). The 3-year overall survival rate was 91% in the surgery plus chemotherapy group and 62% in the chemotherapy-alone group (P < .001). The predominant pattern in the chemotherapy group was local relapse (27.6%). When rituximab was used with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), there was no improvement of the outcomes in patients treated with primary surgical resection. The QOL of patients who underwent surgery and chemotherapy was lower than chemotherapy alone, but its difference was acceptable. Multivariate analysis showed that surgical resection plus chemotherapy was an independent prognostic factor for overall survival. Surgical resection followed by chemotherapy might be an effective treatment strategy with acceptable QOL deterioration for localized intestinal DLBCL. This study was registered at www.clinicaltrials.gov as #NCT01043302.

Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL)

BackgroundPrimary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.MethodsWe retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.ResultsB-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.ConclusionsThe survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.

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.

Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

BackgroundWe performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection.MethodsOf the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria.ResultsOf the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04).ConclusionPrognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.

Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B‐cell lymphoma (DLBCL).

Phase II Study of Gemcitabine Combined with Uracil-Tegafur in Metastatic Pancreatic Cancer

Objective: The single agent gemcitabine is the standard first-line treatment for advanced pancreatic cancer. Recent studies of a combination of gemcitabine and 5-fluorouracil (5-FU) revealed that survival data were superior to those with gemcitabine or 5-FU alone. The administration of oral uracil-tegafur (UFT) is more convenient and simulates the effect of a continuous or protracted infusion of 5-FU. Therefore, we conducted a phase II study of gemcitabine combined with UFT in metastatic pancreatic cancer patients and assessed the efficacy and the toxicity of the regimen. Methods: Twenty-two pancreatic adenocarcinoma patients (18 males, 4 females) were enrolled from December 2000 to September 2002. The regimen consisted of gemcitabine 1,000 mg/m2 once weekly for 3 consecutive weeks, and oral UFT 390 mg/m2/day (in 3 divided doses) on days 1–14. The cycle was repeated every 28 days. The objective tumor response was evaluated after 2 courses of chemotherapy. Results: 82 cycles were administered in total, with a median of 3 cycles per patient (range 1–6 cycles). The median age was 52 years (range 28–69 years). Response to treatment could be assessed in all patients. The objective response rate was 22.7% (95% CI, 7.8–45.4) with no complete response and 5 partial responses. Four patients (18.2%) had stable disease and 13 patients (59.1%) had a progression. The median time to progression was 4.2 months (range 0.9–13.6). The median overall survival was 5.8 months (range 0.5–13.6). Of 10 patients eligible for the assessment of clinical benefit response, 4 (40%, 95% CI 12.2–73.8) showed clinical benefit. Among 21 patients with baseline CA 19-9 levels, CA 19-9 was reduced by 50% or more in 12 patients (57.1%). The chemotherapy was generally well tolerated and the most common grade 3–4 toxic side effects were neutropenia (18.2%), anemia (4.5%), and diarrhea (4.5%). Conclusion: The combination chemotherapy with gemcitabine and UFT in metastatic pancreatic cancer was tolerable for most patients but showed modest response rates and clinical benefit. However, a randomized phase III study should be conducted in order to further test the efficacy of the regimen.

Clinical characteristics, pathological distribution, and prognostic factors in non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study

Background/Aims In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyers ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively. Methods From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL. Results The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age ≥ 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival. Conclusions DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age ≥ 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.

Clinical significance of the preoperative platelet count and platelet-to-lymphocyte ratio (PLT-PLR) in patients with surgically resected non-small cell lung cancer

Background The aim of this study was to assess the prognostic significance of the preoperative platelet count (PLT) and platelet-to-lymphocyte ratio (PLR) in patients with surgically resected non-small-cell lung cancer (NSCLC). Patients and Methods We retrospectively reviewed 202 patients treated for NSCLC between January 2002 and December 2007. Preoperative PLT and PLR scores were calculated using data obtained at the time of admission. Patients were assigned a PLT-PLR score of 0, 1, or 2 based upon the presence of thrombocytosis, an elevated PLR, or both. Results Patients with a PLT-PLR score of 2 had a significantly lower median overall survival (OS) [12.715 mo; 95% confidence interval (CI) 1.215-24.215] when compared with patients with PLT-PLR scores of 1 (52.238 mo; 95% CI 17.062-87.414, p = 0.002) or 0 (not reached, p < 0.001). Relapse-free survival (RFS) was also significantly decreased in patients with a PLT-PLR score of 2 (10.107 mo; 95% CI 3.388-16.826) relative to patients with a PLT-PLR score of 1 (27.214 mo; 95% CI 0-56.253, p = 0.002) or 0 (58.893 mo; 95% CI 32.938-84.848, p < 0.001). In multivariate analysis, a PLT-PLR score of 2 was an independent prognostic factor for poor OS (hazard ratio (HR) 3.473; 95% CI 1.765-6.835, p < 0.001) and RFS (HR 2.286; 95% CI 1.243-4.206, p = 0.008) compared with a PLT-PLR score of 0. Conclusions Preoperative PLT-PLR scores can be useful for predicting disease prognosis in patients with surgically resected NSCLC. Further large prospective studies will be necessary to validate our findings.