Predictors of high score patient-reported barriers to controlling cancer pain: a preliminary report.

PURPOSE: Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient's part can cause major obstacles in pain management. METHOD: We evaluated factors associated with patient's high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory--Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed. RESULTS: The patients were from nine oncology clinics in university hospitals and a veterans' hospital in South Korea. The median pain score (0-10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale. CONCLUSIONS: Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.

Clinical features and course of brain metastases in triple-negative breast cancer: comparison with human epidermal growth factor receptor 2-positive and other type at single institution in Korea.

The incidences and clinical aggressiveness of intracranial metastases have not been as well characterized in patients with triple-negative (TN) breast cancer as in patients with human epidermal growth factor 2-positive (HER2+) breast cancer. Patients diagnosed with brain metastases from primary breast cancer, as determined by computed tomography and/or magnetic resonance imaging, at Asan Medical Center from January 1990 to July 2006 were identified and classified into three subtypes: TN, HER2+, and other. The clinical features and outcomes of these three groups were compared. Of the 7,872 patients diagnosed with primary breast cancer, 198 developed brain metastases; of these, 61 patients with unknown estrogen receptor, progesterone receptor, and HER2 status were excluded. Of the remaining 137 patients, 44 (32%) were classified as TN, 69 (50%) as HER2+, and 24 (18%) as other. Clinical parameters, including performance status and previous adjuvant chemotherapy and/or radiotherapy, were well balanced among groups, except that earlier staged tumors (I and II) were more prevalent in the TN than in the HER2+ and other (59 vs. 36 vs. 38%, P = 0.01). At a median follow-up of 99 months, the median times from initial diagnosis to brain metastasis (20 vs. 32 vs. 45 months, P = 0.01) and to first distant metastasis at any site (16 vs. 23 vs. 23 months, P = 0.005) were significantly shorter in TN than in the HER2+ and other. Median overall survival (OS) from primary cancer diagnosis was significantly shorter in the TN than in the HER2+ and other (31 vs. 39 vs. 57 months, P = 0.02), but survival after brain metastasis was similar (5.9 vs. 5.2 vs. 8.8 months, P = 0.31). Compared with other breast cancer phenotypes, TN breast cancer was characterized by earlier brain and other distant metastases and shorter OS, despite a higher proportion of tumors diagnosed at early stages.

Initial cytoreductive treatment with thalidomide plus bolus vincristine/doxorubicin and reduced dexamethasone followed by autologous stem cell transplantation for multiple myeloma.

BACKGROUND: High-dose chemotherapy supported by autologous stem cell transplantation (ASCT) after combined chemotherapy with infusional vincristine/doxorubicin plus dexamethasone is effective in multiple myeloma (MM). Outpatient treatment with bolus vincristine/doxorubicin infusion plus dexamethasone is convenient and has acceptable efficacy and toxicity for MM. Thalidomide has recently been shown to have significant antimyeloma activity. We assessed the efficacy and toxicity of the combination of bolus vincristine/doxorubicin and reduced dose dexamethasone with thalidomide (T-bVAd), administered on an outpatient basis, in untreated MM. PATIENTS AND METHODS: Twenty-six patients prospectively received T-bVAd, consisting of intravenous (i.v.) vincristine 0.4 mg plus doxorubicin 9 mg/m(2), administered as a single bolus on days 1 to 4, dexamethasone 20 mg per os daily for 4 days, and thalidomide 200 mg/day at bedtime. Response assessment was conducted after each 4-week treatment cycle. Patients who achieved response were allowed to proceed to high-dose chemotherapy with ASCT. RESULTS: On an intention-to-treat basis, 23 of the 26 patients (88%) responded to treatment, with 16 (61%) achieving complete response (CR), 2 (8%) very good partial response (VGPR) and 5 (19%) partial response. Only three patients (12%) were rated as non-responders. Grade 3 and 4 hematologic toxicities consisted of neutropenia (13%), febrile neutropenia (6%), and thrombocytopenia (4%), without significant nonhematologic events. Of the 23 patients who showed response, 7 proceeded to single ASCT and 9 to tandem ASCT. With median follow-up time of 15.3 months (range, 9-25 months), median event free survival (EFS) and overall survival (OS) have not been reached yet, and OS and EFS rates for patients who achieved complete response after T-bVAd regimen were significantly higher than patients not. CONCLUSIONS: Induction therapy with T-bVAd, administered as an outpatient regimen, was efficient and relatively well tolerated in the treatment of MM.

Pilot study for the Psychometric Validation of the Sheffield Profile for Assessment and Referral to Care (SPARC) in Korean Cancer Patients.

PURPOSE: This study aimed to validate the Sheffield Profile for Assessment and Referral to Care (SPARC) as an effective tool for screening palliative care needs among Korean cancer patients. MATERIALS AND METHODS: The English version of the SPARC was translated by four Korean oncologists and reconciled by a Korean language specialist and a medical oncologist fluent in English. After the first version of the Korean SPARC (K-SPARC) was developed, back-translation into English was performed by a professional translator and bilingual oncologist. The back-translated version was reviewed by the original author (S.H.A.), and modifications were made (ver. 2). The second version of the K-SPARC was tested against other questionnaires, including the Functional Assessment of Cancer Therapy-General (FACT-G) and the Edmonton Symptom Assessment System (ESAS). RESULTS: Thirty patients were enrolled in the pilot trial. Fifteen were male, and the median age was 64.5 years. Six patients had an Eastern Cooperative Oncology Group performance status of 2 or more. All patients except one were receiving chemotherapy. Regarding internal consistency, the Cronbach's α scores for physical symptoms, psychological issues, religious and spiritual issues, independency and activity, family and social issues, and treatment issues were 0.812, 0.804, 0.589, 0.843, 0.754, and 0.822, respectively. The correlation coefficients between the SPARC and FACT-G were 0.479 (p=0.007) for the physical domain and -0.130 (p=0.493) for the social domain. CONCLUSION: This pilot study indicates that the K-SPARC could be a reliable tool to screen for palliative care needs among Korean cancer patients. A further study to validate our findings is ongoing.

Yttrium-90-ibritumomab tiuxetan in combination with intravenous busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

BACKGROUND: Radiolabelled immunotherapy agents have an increasingly significant role in autologous stem cell transplantation (ASCT) by improving the tolerability and increasing the efficacy of the conditioning regimen, thereby reducing the relapse risk. We evaluated the efficacy and safety of yttrium-90-ibritumomab tiuxetan ((90)Y-ibritumomab) combined with intravenous busulfan, cyclophosphamide, and etoposide (Bu/Cy/E) followed by ASCT in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). METHODS: Each patient received a single dose of (90)Y-ibritumomab (0.4 mCi/kg on day -14) with Bu/Cy/E as a conditioning regimen. RESULTS: The patient cohort consisted of 19 individuals (ten males), of median age 51 years (range, 25-63 years). Sixteen patients had received two or more chemotherapy regimens before transplantation. Histologies were diffuse large B-cell (n = 14), follicular (n = 2), mantle cell (n = 2), and Burkitt lymphoma (n = 1). All patients engrafted. The median time to neutrophil engraftment was 10 days and time to platelet engraftment was 10 days. Nineteen patients were evaluable for response. The objective overall response rate was 84.2% (16/19): continued CR, 36.8% (7/19); induced CR, 36.8% (7/19); and PR, 10.5% (2/19). With a median follow-up of 29.4 months (13.4-36.6), the estimated 3-year overall survival and event-free survival rates were 52.6% (95% confidence interval [CI] 45.8-59.4) and 26.3% (95% CI 19.8-32.8), respectively. Adverse events were similar to those seen historically with Bu/Cy/E alone, and there were no treatment related deaths. CONCLUSION: In conclusion, (90)Y-ibritumomab with Bu/Cy/E and ASCT is feasible in patients with relapsed or refractory B-cell NHL, without increased toxicity.

Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin's lymphoma.

BACKGROUND: Lymphocyte recovery after autologous stem cell transplantation (ASCT) has been shown to be associated with positive clinical outcome in non-Hodgkin's lymphoma (NHL). This study sought to identify variables that affect lymphocyte recovery and survival after ASCT. STUDY DESIGN AND METHODS: A retrospective analysis of outcomes in 97 consecutive patients with NHL who underwent ASCT in a single center from August 1999 to January 2008 was conducted. RESULTS: A significant relationship was not observed between infused lymphocyte count and days to recovery of absolute lymphocyte count 500 x 10(6)/L or greater after ASCT (ALC500; r = 0.139, p = 0.176), but there was a significant inverse correlation between infused CD34+ cell count and days to ALC500 (r = -0.333, p = 0.001). Univariately, infused CD34+ cell count and recovery of ALC500 by 20th day after ASCT were significant predictors of survival. The median overall survival (OS) and event-free survival (EFS) were significantly longer in patients who received 8.2 x 10(6) CD34+ cells/kg or more than in those who received fewer than 8.2 x 10(6) CD34+ cells/kg (OS, not reached vs. 11.6 months, p = 0.001; EFS, not reached vs. 4.8 months, p = 0.003). Multivariate analysis confirmed that infused CD34+ cell count was an independent prognostic factor for OS (p = 0.017) and EFS (p = 0.002). CONCLUSION: These data suggest that infused CD34+ cell count is predictive of kinetics of lymphocyte recovery after ASCT and is an independent prognostic factor for OS and EFS after ASCT in patients with NHL.

Dose escalation of imatinib after failure of standard dose in Korean patients with metastatic or unresectable gastrointestinal stromal tumor.

OBJECTIVE: We evaluated the results of imatinib dose escalation in patients with advanced gastrointestinal stromal tumors (GISTs) after disease progression on standard-dose imatinib. METHODS: Clinical data from patients with metastatic or unresectable GISTs whose dose of imatinib was increased after disease progression on imatinib 400 mg/day were retrospectively reviewed. RESULTS: The 24 patients studied had a median age of 52 years. Imatinib dosing was escalated to 600 mg/day in 12 patients, then to 800 mg/day in four patients. The other 12 patients had dose escalation directly to 800 mg/day. Two patients (8.3%) achieved a partial response, and seven (29.2%) had stable disease. Six-month progression-free and overall survival rates were 33.3 and 70.7%, respectively. Dose escalation to 600 or 800 mg/day was generally well tolerated. CONCLUSION: Imatinib dose escalation is feasible and well tolerated in patients with advanced GIST who progress on standard-dose therapy, producing clinical benefit in approximately 37% of patients.

BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients: comparative analysis of efficacy and toxicity.

The treatment of choice for relapsed/refractory non-Hodgkin's lymphoma (NHL) consists of high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Little is known, however, regarding the comparative toxicity and efficacy of various HDC regimens applied in NHL. We have retrospectively evaluated the clinical aspects of the BCNU, etoposide, cytarabine, and cyclophosphamide (BEAC) and BCNU, etoposide, cytarabine, and melphalan (BEAM) regimens for ASCT. Between April 1994 and February 2005, 97 NHL patients underwent HDC with BEAC (N = 69) or BEAM (N = 28), followed by ASCT, at the Asan Medical Center. We matched each BEAM patient with two BEAC patients having the same International Prognostic Index. Thus, 84 patients (56 BEAC and 28 BEAM) were analyzed. Median age was 40.5 years, and baseline characteristics were well balanced between the two groups. The median time to neutrophil engraftment (>500/mm(3)) was significantly longer with BEAC than with BEAM (12 vs 11 days, P = 0.001), as was the total amount of red blood cell transfusion (6.5 vs 3.7U, P = 0.037), but the median time to platelet engraftment (>20,000/mm(3)) and the total amount of platelet transfusion did not differ between the two groups. BEAM patients had significantly more frequent World Health Organization grade greater than or equal to 2 diarrhea than BEAC patients (46.4 vs 19.6%, P = 0.010), but the incidence of mucositis, nausea/vomiting, and bleeding and the number of episodes of febrile neutropenia and septicemia did not differ between the two groups. Median follow-up for survivors was 33 months in the BEAM group and 89 months in the BEAC group. Median overall survival and median event-free survival were not reached in the BEAM group and were 7.9 (95% confidence interval [CI], 1-14.8 months, P = 0.003) and 3.7 months (95% CI, 0.1-7.2 months, P = 0.001), respectively, in the BEAC group. BEAM appeared to be superior to BEAC for survival. Regimen-related toxicities were similar, except that BEAM was associated with more frequent but acceptable diarrhea.

A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer.

PURPOSES: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer. METHODS: Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1-7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m2; level 2, 85/120/80 mg/m2; level 3, 85/120/100 mg/m2; level 4, 85/150/100 mg/m2; and level 5, 85/180/100 mg/m2. Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity. RESULTS: Twenty-four patients were enrolled between October 2012 and February 2014 (median age 59 years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6 %. CONCLUSIONS: The combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan, and 100 mg/m2 of S-1 every 2 weeks.

The Clinical Utility of FDG PET-CT in Evaluation of Bone Marrow Involvement by Lymphoma.

PURPOSE: Bone marrow biopsy is a standard method for the evaluation of bone marrow infiltration by lymphoma; however, it is an invasive and painful procedure. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is a noninvasive imaging technique with the potential to detect bone marrow involvement by lymphoma. MATERIALS AND METHODS: We retrospectively reviewed medical records of lymphoma patients. All patients were examined by FDG PET-CT and iliac crest bone marrow biopsy for initial staging work-up. RESULTS: The study population comprised 94 patients (median age, 60 years; 56 males) with Hodgkin's lymphoma (n=8) or non-Hodgkin's lymphoma (n=86). Maximum standardized uptake values on the iliac crest of patients with lymphoma infiltrated bone marrow were significantly higher than those of patients with intact bone marrow (2.2±1.2 g/mL vs. 1.3±0.4 g/mL; p=0.001). The calculated values for FDG PET-CT during evaluation of bone marrow involvement were as follows: sensitivity 50%, specificity 96%, positive predictive value 80%, negative predictive value 85%, and positive likelihood ratio (LR+) 11.7. The value of LR+ was 16.0 in patients with aggressive subtypes of non-Hodgkin's lymphoma (NHL). CONCLUSION: FDG PET-CT could not replace bone marrow biopsy due to the low sensitivity of FDG PET-CT for detection of bone marrow infiltration in lymphoma patients. Conversely, FDG PET-CT had high specificity and LR+; therefore, it could be a useful tool for image-guided biopsy for lymphoma staging, especially for aggressive subtypes of NHL. In addition, unilateral bone marrow biopsy could be substituted for bilateral bone marrow biopsy in lymphoma patients with increased FDG uptake on any iliac crest.

Randomized phase 2 trial of S1 and oxaliplatin-based chemoradiotherapy with or without induction chemotherapy for esophageal cancer.

PURPOSE: To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. PATIENTS AND METHODS: Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. RESULTS: A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. CONCLUSIONS: Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

Usefulness of combined PET/CT to assess regional lymph node involvement in gastric cancer.

AIMS AND BACKGROUND: The aim of this study was to evaluate the value of positron emission tomography/computed tomography (PET/CT) for preoperative staging of gastric cancer and to compare the diagnostic performance of PET/CT with that of contrast-enhanced computed tomography (CECT). METHODS: We retrospectively reviewed 74 gastric cancer patients who underwent preoperative PET/CT and CECT, and subsequent curative surgical resection between April 2007 and July 2011. Preoperative PET/CT and CECT images for primary tumors of the stomach and lymph node metastases were reviewed retrospectively. The final diagnoses of primary tumors and LN metastases were based on histopathological specimens in all patients. RESULTS: Advanced gastric cancer was present in 65% of patients (n = 48), and the remaining patients had early gastric cancer (n = 26). Sixteen patients (22%) showed signet-ring-cell histology. For the detection of the primary tumor, the sensitivity of PET/CT was significantly higher than that of CECT (67% vs 55%, respectively; P = 0.049). For the evaluation of regional lymph node metastasis, the sensitivity, specificity, and accuracy of PET/CT and CECT were 34% and 51% (P = 0.065), 88% and 79% (P = 0.687), and 58% and 64% (P = 0.332), respectively. Neither PET/CT nor CECT detected regional lymph node metastases in early gastric cancer patients. Signet-ring-cell histology showed trends of non-FDG-avid lymph node metastases (odds ratio = 0.15, 95% confidence interval 0.17-1.37, P = 0.093). CONCLUSIONS: The accuracy of PET/CT is low and it is not a useful tool in the staging of gastric cancer overall in early gastric cancer and in signet-ring-cell carcinoma. Furthermore, the sensitivity of PET/CT could be inferior to that of CECT in the diagnosis of regional lymph node metastasis.

Phase II trial of gemcitabine and S-1 for patients with advanced pancreatic cancer.

PURPOSE: To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer. METHODS: This study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14 every 21 days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40 mg bid (total 80 mg/day) for a BSA of <1.25, 50 mg bid (total 100 mg/day) for a BSA of ≥1.25 but <1.5, and 60 mg bid (total 120 mg/day) for a BSA of ≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival. RESULTS: Thirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5 % [95 % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally mild. CONCLUSIONS: Combination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

A Phase II Study to Evaluate the Efficacy of Ramosetron, Aprepitant, and Dexamethasone in Preventing Cisplatin-Induced Nausea and Vomiting in Chemotherapy-Naïve Cancer Patients.

PURPOSE: Combination therapy with aprepitant, serotonin receptor antagonist, and steroids improves the complete response rate of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, it is not known whether ramosetron is suitable for administration in combination with aprepitant. Therefore, we conducted a multicenter, open-label, prospective, phase II study in order to assess the efficacy and tolerability of combination therapy with ramosetron, aprepitant, and dexamethasone (RAD) for prevention of cisplatin-based CINV in chemotherapy-naïve patients with solid cancers. MATERIALS AND METHODS: Forty-one patients with various solid cancers (31 male and 10 female; median age, 59 years) who received treatment with highly emetogenic chemotherapy (median cisplatin dose, 70 mg/m(2); range 50 to 75 mg/m(2)) were enrolled in this study. Oral aprepitant (125 mg on day 1; 80 mg on days 2 and 3), intravenous ramosetron (0.6 mg on day 1), and oral dexamethasone (12 mg on day 1; 8 mg on days 2-4) were administered for prevention of CINV. RESULTS: The complete response (no emesisand retching and no rescue medication) rate was 94.9% in the acute period (24 hours post-chemotherapy), 92.3% in the delayed period (24-120 hours post-chemotherapy), and 92.3% in the overall period (0-120 hours). The absolute complete response (complete response plus no nausea) rate was 74.4% in the acute period, 51.3% in the delayed period, and 46.2% in the overall period. There were no grade 3 or 4 toxicities related to these antiemetic combinations. CONCLUSION: RAD regimen is a safe and effective antiemetic treatment for prevention of CINV in patients receiving highly emetogenic chemotherapy.

A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas.

BACKGROUND: Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14). METHODS: Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m(2) bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study. RESULTS: Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m(2). In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy. CONCLUSION: Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.

Addition of rituximab to the CHOP regimen has no benefit in patients with primary extranodal diffuse large B-cell lymphoma.

BACKGROUND: The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP) has significantly improved clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL). However, new predictors of patient response to R-CHOP have not been established. We aimed to evaluate the impact of R-CHOP compared with CHOP in patients with DLBCL and to establish clinical predictors of better outcomes in these patients. METHODS: We retrospectively identified 177 patients diagnosed with CD20-positive DLBCL and treated with CHOP (N=82) or R-CHOP (N=95). The response rate, event-free survival (EFS), and overall survival (OS) rates were compared between the 2 treatment groups. All patients were classified into primary extranodal lymphoma (PENL) or nodal lymphoma (NL) subgroups, and the clinical parameters of each subgroup were analyzed. RESULTS: The overall response rate was higher in R-CHOP group (95% vs. 84%, P=0.07). The 3-year EFS rate was significantly higher in R-CHOP group (71% vs. 52%, P=0.013), but the OS rate was comparable between the 2 groups (79% vs. 69%, P=0.23). A significant survival benefit was seen with R-CHOP compared to CHOP therapy in NL patients (P=0.002 for EFS and 0.04 for OS). Multivariate analyses confirmed that R-CHOP therapy is an independent prognostic factor for EFS (hazard ratio of 0.32 [0.17-0.62], P=0.001) and OS (hazard ratio of 0.4 [0.18-0.87], P=0.02) in NL patients. CONCLUSION: Patients in the PENL group did not benefit from R-CHOP chemotherapy.

A phase II study of mitomycin-C and S-1 as third-line chemotherapy in patients with advanced colorectal cancer.

This study was conducted to evaluate the efficacy and safety of the combination of mitomycin-C (MMC) and S-1 as third-line chemotherapy for patients with advanced colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens. Patients were recruited into the study from January 2009 and 10 patients were enrolled for 10 months. However, since no patients had shown a response by 10 months, the study was terminated early according to the protocol. MMC 7 mg/m(2) was administered intravenously on day 1 every 6 weeks in the first 4 cycles. S-1 was administered twice daily at 35 mg/m(2), within 1 h of meals on days 1-14. Following a rest for 7 days, S-1 was administered again on days 22-35, followed by a 7-day rest. A total of 14 cycles were delivered for 10 patients. All 10 patients were assessable for response. A total of 3 patients (30%) had stable disease and the remaining 7 showed disease progression. With a median follow-up of 7 months, the median overall survival was 10.5 months. Grade 3-4 myelotoxicities included neutropenia in two patients, anemia in two and thrombocytopenia in one. Grade 1-2 nausea and vomiting developed in 5 patients. One patient experienced grade 3 diarrhea. Grade 1-2 hand-foot syndrome occurred in 4 patients. In conclusion, the combination of MMC and S-1 as third-line chemotherapy in patients with advanced CRC appears to be well tolerated but has poor activity.

Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated advanced gastric cancer.

BACKGROUND: We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC). METHODS: Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle. RESULTS: In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle. CONCLUSIONS: The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.

A phase II study of pemetrexed and carboplatin as a salvage therapy for platinum-pretreated patients with non-small cell lung cancer.

BACKGROUND: Although platinum-based doublet chemotherapy is considered as standard of care for patients with advanced non-small cell lung cancer (NSCLC), most of them are eventually supposed to experience disease progression. Pemetrexed, docetaxel, erlotinib, and gefitinib have been shown to be active as monotherapy for pretreated patients. In this study, the efficacy of pemetrexed and carboplatin as a salvage therapy for patients with advanced NSCLC is evaluated. PATIENTS AND METHODS: From March 2007 to February 2009, 32 patients who were diagnosed with inoperable NSCLC and treated with one or more prior cisplatin-based chemotherapies were enrolled. Treatment consisted of pemetrexed 500 mg/m(2) over a 10-min intravenous infusion and carboplatin at an AUC 5 mg/mL/min over a 30-min intravenous infusion on Day 1 of a 21-day cycle. All patients were supplemented with folic acid and vitamin B12 to reduce the hematological toxicity of pemetrexed. RESULTS: There were one (3.1%) complete response and five partial (15.6%) responses. The overall response rate was 18.8% and the median response duration was 4.4 months. Among the responders, four patients had adenocarcinoma and two had squamous cell carcinoma. Nine patients had stable disease, and the disease control rate was 46.9%. With a median follow up duration of 9.4 months, the median time to progression was 2.3 months and the median OS was 9.4 months. Seven patients (21.9%) experienced grade 3 and 4 hematologic toxicities; one anemia (3.1%), six neutropenia (18.8%), and six thrombocytopenia (18.8%). Two patients experienced grade 4 febrile neutropenia with infection. Four patients (12.5%) experienced grade 3 non-hematologic toxicities; four asthenia (12.5%), two anorexia (6.3%), and one stomatitis (3.1%). Grade 1-2 peripheral neuropathy developed in 13 patients (40.6%). CONCLUSION: The combination of pemetrexed and carboplatin showed favorable toxicity profiles and activity in the pretreated patients with advanced NSCLC. It is suggested that this regimen can be a good chemotherapeutic option as a salvage therapy for patients with NSCLC.

Autologous stem cell transplantation for diffuse large B-cell lymphoma with residual extranodal involvement.

BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL) in Koreans is frequently accompanied by extranodal (EN) disease at the time of autologous stem cell transplantation (ASCT). We sought to determine whether high EN involvement affected survival following ASCT in Koreans. METHODS: We reviewed 27 patients who had DLBCL with residual disease at ASCT: 13 with residual disease at nodal site(s) only and 14 with nodal and EN disease. RESULTS: Univariate analysis showed that disease status, lactate dehydrogenase (LDH), and performance status at ASCT were predictors of survival following ASCT. The number of EN sites, as categorized by the International Prognostic Index system, had no prognostic significance. When EN involvement at ASCT was classified as negative or positive, the 2-year overall survival for the negative group was 64%, significantly better than the 14% for the positive group (p=0.021), and the event-free survival for the negative group was 62%, significantly better than the 14% for the positive group (p=0.02). CONCLUSIONS: Patients who had DLBCL with residual EN involvement at ASCT showed worse outcomes following ASCT compared to those without EN disease.