Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study.

PURPOSE: To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain. MATERIALS AND METHODS: One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator's discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated. RESULTS: A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea. CONCLUSION: HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.

A prospective multicentre phase II study of cisplatin and weekly docetaxel as first-line treatment for recurrent or metastatic nasopharyngeal cancer (KCSG HN07-01).

BACKGROUND: The purpose of this phase II study was to determine the efficacy and toxicity of cisplatin and weekly docetaxel combination chemotherapy as a first-line treatment in patients with recurrent or metastatic nasopharyngeal cancer. PATIENTS AND METHODS: Recurrent or metastatic nasopharyngeal cancer patients were enrolled and received a combination of weekly docetaxel (35 mg/m(2) on Day1 and Day8) and cisplatin (70 mg/m(2) D1) every 21 days, for up to a maximum of 6 cycles. The primary endpoint was objective response rate, and the secondary endpoints included toxicity of combination chemotherapy, progression-free survival, overall survival and 1-year survival rate. RESULTS: In total, 47 patients were enrolled and analysed, and 46 patients (97.9%) completed the planned protocol. In an intent-to-treat analysis, 6 patients (12.8%) achieved complete response (CR) and 27 patients (57.4%) showed partial response (PR), with an objective response rate of 70.2%. The median progression-free survival and overall survival were 9.6 months (95% C.I. 5.7-13.5 months) and 28.5 months (95% C.I. 16.9-40.1 months), respectively, and the 1-year survival rate was 89.9%. The common grade 3 adverse events were stomatitis (1.2%), neutropenia (0.8%), anaemia (0.8%), infection (0.8%) and diarrhoea (0.8%). Grade 4 adverse events were not observed in this study. CONCLUSIONS: The combination chemotherapy of cisplatin and weekly docetaxel is highly effective and shows favourable toxicity as a first-line chemotherapy in patients with recurrent or metastatic nasopharyngeal cancer.

A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: combined analysis with translational research.

BACKGROUND: To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC). METHODS: Locally advanced PC was excluded. Erlotinib was given at a dose of 100 mg daily from D1 to D28. 1000 mg/m(2) of gemcitabine was given on D1,8,15 and 1660 mg/m(2)/day of capecitabine was given from D1 to 21, repeated every 4 weeks. Response was assessed every 8 weeks. RESULTS: A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6-46.6%) and 83.7% (95% CI, 72.7-94.7%) respectively. The PFS was 6.5 months (95% CI, 3.4-9.7) and OS was 12.0 months (95% CI, 8.6-15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA. CONCLUSIONS: Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.

Change in cancer pain management in Korea between 2001 and 2006: results of two nationwide surveys.

CONTEXT: In Korea, many health care professionals have shown increased concern about the management of cancer pain. Five years after a pain management guideline was distributed to Korean physicians, the Korean Society of Hospice and Palliative Care evaluated the change in cancer pain management. The period evaluated was between 2001 and 2006. METHODS: We did a prospective, cross-sectional cancer pain survey on the change of the pain prevalence and pain intensity, its impact on daily activities and the adequacy of pain management between 2001 and 2006. RESULTS: Overall, 7565 patients were enrolled from 72 cancer hospitals in the 2001 cancer pain survey and 7245 patients were enrolled from 63 cancer hospitals in the 2006 cancer pain survey. The overall prevalence of cancer pain and the percentage of patients reporting a negative pain management index were significantly decreased in the 2006 cancer pain survey compared with the 2001 cancer pain survey (44.9% vs. 52.1%, P<0.0001 and 41.6% vs. 45.0%, respectively, P=0.0005). However, in 2006, physicians did not prescribe analgesics to 25.8% of the patients with severe pain and they did not adjust the prescribed analgesics properly in 47.4% of the patients with severe pain. CONCLUSION: Some improvement in cancer pain management was noted during the five years between 2001 and 2006. However, all of the physicians who care for cancer patients should pay more attention to cancer pain management, and an educational program for cancer pain management should be distributed to all of the physicians who care for cancer patients.

Erlotinib monotherapy for stage IIIB/IV non-small cell lung cancer: a multicenter trial by the Korean Cancer Study Group.

BACKGROUND: Erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) is an oral, epidermal growth factor receptor tyrosine kinase inhibitor that has antitumor activity and good tolerability in non-small cell lung cancer (NSCLC). In particular, higher response rates have been reported in Asian patients than in Western patients. The aim of this study conducted by the Korean Cancer Study Group was to evaluate the efficacy and tolerability of erlotinib monotherapy as a palliative treatment for advanced NSCLC patients in Korea. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed stage IIIB or IV NSCLC including recurrent or metastatic disease, with performance status from 0 to 3, were eligible either if they had received any anticancer treatment except epidermal growth factor receptor inhibitors or if they were unsuitable for chemotherapy because of poor performance status. Enrolled patients were treated with oral erlotinib at a dose of 150 mg daily until disease progression or development of intolerable toxicity. RESULTS: A total of 120 patients were enrolled between January 2005 and May 2006. Forty-four patients (36.7%) were female and 72 patients were current or former smoker. Fifty percent of patients had received one prior palliative chemotherapy regimens and 34.2% had two or more prior palliative regimens. The overall tumor response rate was 24.2% (95% confidence interval [CI], 16.8-32.8%) with 4 complete responses and 25 partial responses, and the disease control rate was 56.7%. The favorable clinical variables for tumor response were female (P = 0.001), never smokers (P = 0.041), and adenocarcinoma (P = 0.001). The most common adverse event was skin rash (78% of which grade 3 or 4 skin rash occurred in 13.3% of the patients). With a median follow-up of 23.6 months, the median time to progression was 2.7 months (95% CI, 2.2-3.2), and the median overall survival was 12.9 months (95% CI, 6.9-18.8). By multivariate analysis, female and development of skin rash were significantly associated with longer time to progression and overall survival. CONCLUSION: Erlotinib monotherapy showed significant antitumor activity and an acceptable tolerability profile as a palliative treatment in advanced NSCLC patients in Korea, especially in females, never smokers, and patients with adenocarcinoma histology.

Randomized, multicenter, phase III trial of heptaplatin 1-hour infusion and 5-fluorouracil combination chemotherapy comparing with cisplatin and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

PURPOSE: Heptaplatin (Sunpla) is a cisplatin derivative. A phase IIb trial using heptaplatin resulted in a 34% response rate with mild nephrotoxicity. We conducted a randomized phase III trial of heptaplatin plus 5-FU compared with cisplatin plus 5-FU in patients with advanced gastric cancer. MATERIALS AND METHODS: One hundred seventy-four patients (heptaplatin, n=88; cisplatin, n=86) from 13 centers were enrolled. The eligibility criteria were as follows: patients with pathologically-proven adenocarcinoma, chemonaive patients, or patients who had received only single adjuvant chemotherapy, and who had a measurable or evaluable lesion. On day 1, heptaplatin (400 mg/m(2)) or cisplatin (60 mg/m(2)) was given over 1 hour with 5-FU (1 gm/m(2)) on days 1~5 every 4 weeks. RESULTS: At the time of survival analysis, the median overall survival was 7.3 months in the 5-FU + heptaplatin (FH) arm and 7.9 months in the 5-FU + cisplatin (FP) arm (p=0.24). Of the FH patients, 34.2% (complete response [CR], 1.3%; partial response [PR], 32.9%) experienced a confirmed objective response compared with 35.9% (CR 0%, PR 35.9%) of FP patients (p=0.78). The median-time-to-progression was 2.5 months in the FH arm and 2.3 months in the FP arm. The incidence of neutropenia was higher with FP (28%) than with FH (16%; p=0.06); grade 3~4 nausea and vomiting were more frequent in the FP than in the FH arm (p=0.01 and p=0.05, respectively). The incidence of increased proteinuria and creatininemia was higher with FH than with FP; however, there was no statistical difference. There were no treatment-related deaths. CONCLUSION: Heptaplatin showed similar effects to cisplatin when combined with 5-FU in advanced gastric cancer patients with tolerable toxicities.

Gemcitabine, etoposide, cisplatin, and dexamethasone in patients with refractory or relapsed non-Hodgkin's lymphoma.

BACKGROUND/AIMS: To date, an effective salvage chemotherapy regimen for the treatment of refractory or relapsing non-Hodgkin's lymphoma (NHL) has not been discovered. This study was conducted to evaluate the efficacy and safety of gemcitabine, etoposide, cisplatin, and dexamethasone in relapsed or refractory NHL patients. METHODS: All patients had histologically proven relapsed or refractory NHL. Treatments consisted of gemcitabine 700 mg/m(2) by continuous i.v. on days 1 and 8; etoposide 40 mg/m(2) by i.v. on days 1-4; cisplatin 60 mg/m(2) by i.v. on day 1; or dexamethasone 40 mg by i.v. on days 1-4 (GEPD) every 21 days. The primary end point was the patient response rate following two cycles of treatment. After two cycles, stem cells were harvested using mobilizing regimens (ESHAP or GEPD plus filgrastim), and this was followed by autologous stem cell transplantation or four additional cycles of GEPD. RESULTS: Between January 2005 and January 2006, 20 patients (13 males and 7 females) were enrolled in the study. The median age was 53 (range 16-75) years. The most common histology was diffuse large B-cell lymphoma (n=10). The median follow-up duration was 5.2 (range 1.0-16.0) months. After two cycles, the overall response rate was 50.0% (10/20), including two complete responses and eight partial responses. The dose-limiting toxicity was myelosuppression. Grade IV neutropenia and thrombocytopenia occurred in 13 (65.0%) and 6 patients (30.0%), respectively. The median number of CD34-positive cells collected was 6.0 (range, 2.8-11.6)x10(6)/kg. Of the 17 patients < 66 years of age, 4 (23.5%) proceeded to autologous stem cell transplantation. CONCLUSIONS: GEPD chemotherapy in patients with refractory or relapsed NHL was effective as a salvage therapy and helpful for stem cell harvest followed by autologous transplantation.

TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin.

PURPOSE: The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with advanced gastric cancer. PATIENTS AND METHODS: Fifty-seven patients with advanced gastric cancer treated with paclitaxel and cisplatin combination chemotherapy were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue, and the single nucleotide polymorphisms (SNPs) of ten apoptosis-related genes [LTA, TP53, BCL2L11, BID, FASL, caspase 3, caspase 6, caspase 7, and caspase 9] determined using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The Arg/Pro and Pro/Pro genotypes of TP53 codon 72 were significantly correlated with a lower response rate to the combination chemotherapy when compared to the Arg/Arg genotype (35.7 vs. 66.7%, P-value 0.019) in a logistic regression analysis. A multivariate survival analysis also showed that the time to progression for the patients with the Arg/Pro and Pro/Pro genotypes of TP53 codon 72 was worse than for the patients with the Arg/Arg genotype (Hazard ratio = 3.056, P-value = 0.047), whereas the overall survival was not significantly different. CONCLUSION: The TP53 codon 72 SNP was found to be predictive of the response to chemotherapy and correlate with the time to progression in patients with advanced gastric cancer treated with paclitaxel and cisplatin chemotherapy.

Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer?

PURPOSE: This study investigated possible molecular predictors of outcome in Korean patients with advanced non-small cell lung cancer treated with erlotinib. EXPERIMENTAL DESIGN: One hundred and twenty patients received erlotinib and were followed prospectively. Ninety-two tissue samples were analyzed for epidermal growth factor receptor (EGFR) gene mutations (exons 18, 19, and 21), 88 for EGFR gene amplification by real-time PCR, and 75 for EGFR protein expression by immunohistochemistry. RESULTS: The overall tumor response rate was 24.2% (complete response, 4; partial response, 25) with 56.7% of disease control rate. With a median follow-up of 23.6 months, the median time to progression (TTP) was 2.7 months and the median overall survival was 12.9 months. EGFR gene mutations were found in 26.1% (24 of 92), EGFR gene amplification in 40.9% (36 of 88), and EGFR protein expression in 72% (54 of 75). There was a strong association between EGFR gene mutations and gene amplification (gamma = 0.241). Patients with EGFR gene mutations or gene amplification showed both better response rate (58.3% versus 16.2%, P < 0.001; 41.7% versus 17.3%, P = 0.012) and TTP (8.6 versus 2.5 months, P = 0.003; 5.8 versus 1.8 months, P < 0.001) and overall survival (not reached versus 10.8 months, P = 0.023; not reached versus 10.1 months, P = 0.033). By multivariate analysis, EGFR gene mutation was the only significant molecular predictor for TTP (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89). CONCLUSIONS: Our findings indicate that EGFR gene mutation is a more predictive marker for improved TTP than EGFR gene amplification in erlotinib-treated Korean non-small cell lung cancer patients. Prospective studies from diverse ethnic backgrounds are required to determine the exact role of these molecular markers.

Treatment outcomes with CHOP chemotherapy in adult patients with hemophagocytic lymphohistiocytosis.

The objective of the current study was to investigate the treatment outcomes for the use of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy in adult patients with hemophagocytic lymphohistiocytosis (HLH). Seventeen HLH patients older than 18 yr of age were treated with CHOP chemotherapy. A response evaluation was conducted for every two cycles of chemotherapy. With CHOP chemotherapy, complete response was achieved for 7/17 patients (41.2%), a partial response for 3/17 patients (17.6%), and the overall response rate was 58.8%. The median response duration (RD) was not reached and the 2-yr RD rate was 68.6%, with a median follow-up of 100 weeks. Median overall survival (OS) was 18 weeks (95% CI, 6-30 weeks) and the 2-yr OS rate was 43.9%. Reported grade 3 or 4 non-hematological toxicities were increased serum liver enzyme levels and stomatitis. Grade 3 or 4 hematological toxicities were leukopenia (50.8%), anemia (20%), and thrombocytopenia (33.9%). Neutropenic fever was observed in 21.6% of patients (14/65 cycles), and most of the cases were resolved with supportive care including treatment with broad-spectrum antibiotics. CHOP chemotherapy seems to be effective in adult HLH patients and the toxicities are manageable.

Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas: a phase II study.

PURPOSE: The present study was conducted to evaluate the safety and efficacy of alemtuzumab plus CHOP chemotherapy for patients with peripheral T-cell lymphomas (PTCLs). PATIENTS AND METHODS: Twenty patients with newly diagnosed PTCLs were enrolled. The treatment consisted of classical CHOP plus alemtuzumab (10 mg i.v. on day 1 and 20 mg i.v. on day 2 in the first cycle, then 30 mg i.v. on day 1 in the subsequent cycles) based on 3-week intervals. RESULTS: Thirteen complete responses (65.0%) and three partial responses (15.0%) were confirmed, giving an overall response rate of 80.0%. The estimated event-free survival at 1 year was 43.3%. The most severe hematologic adverse event was neutropenia, which occurred with a grade-4 intensity in 18 patients (90.0%). Also, febrile neutropenia was observed in 11 patients (55.0%). Five patients (25%) experienced cytomegalovirus (CMV) reactivation, while three patients developed CMV diseases, such as pneumonitis or retinitis. There were two treatment-related deaths. Based on the high incidence of the adverse infectious and hematologic events, the current study was closed after 20 of the planned 43 patients had been enrolled. CONCLUSION: The alemtuzumab plus CHOP chemotherapy seemed to produce active antitumor activity in terms of the complete response rates in patients with PTCLs. However, since high infectious and hematologic toxicities were observed, careful monitoring and early treatment are needed to prevent treatment-related mortality.

Multicenter phase II study of weekly paclitaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer.

PURPOSE: Since a weekly administration of paclitaxel has demonstrated a sustained efficacy and more favorable toxicity profile than a 3-weekly administration for various solid tumors, the present study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus cisplatin in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 100 mg/m(2) plus cisplatin 35 mg/m(2) on days 1 and 8 based on a 3-week cycle. RESULTS: Fifty-two patients were enrolled in the current study. Two complete responses and 17 partial responses were confirmed, giving an overall response rate of 36.5%. At a median follow-up of 8.5 months, the median time to progression and median overall survival was 6.0 and 10.8 months, respectively. Grade 3 neutropenia occurred in ten patients, while no grade 4 neutropenia or febrile neutropenia was observed. The most common non-hematologic toxicity was nausea (grade 1/2, 56.9%). There were no treatment-related deaths. CONCLUSION: A weekly paclitaxel and cisplatin combination was found to be well-tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.

Induction chemotherapy of docetaxel and Cisplatin for the elderly patients with squamous cell carcinoma of the head and neck.

PURPOSE: Although concurrent chemoradiotherapy (CCRT) has been considered as a standard treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN), this treatment is associated with increased toxicities such as mucositis and dermatitis. As a result, the dose intensity can be reduced and interruptions of radiotherapy are more common for CCRT than for sequential treatment, especially for the elderly patients. This prospective study was performed to assess the efficacy and safety profiles of the induction chemotherapy of docetaxel and cisplatin for elderly patients with locally advanced SCCHN. MATERIALS AND METHODS: Patients over 65 years of age with locally advanced SCCHN were treated with docetaxel (70 mg/m(2)) and cisplatin (75 mg/m(2)) every 21 days. The chemotherapy consisted of two cycles with a third cycle that was administered to the responding patients. Patients who did not respond to initial chemotherapy underwent radiotherapy as a definitive local treatment. RESULTS: Fifty patients were enrolled in this study and 44 patients were assessable for response and toxicity. The overall response rate was 88%, 16 patients (36%) achieved a complete response and 23 patients (52%) achieved a partial response. After a median follow-up of 24 months (range: 9 approximately 38 months) the median disease free period and overall survival period had not yet been reached. The one year and two year survival rates were 89% and 70%, respectively. The most common grade 3/4 adverse event was neutropenia, which occurred in 33 patients (75%) and 4 patients had febrile neutropenia. CONCLUSION: Combination chemotherapy of docetaxel and cisplatin is an effective regimen with an acceptable safety profile as the induction treatment for elderly patients suffering with SCCHN.

CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas.

OBJECTIVE: The present study evaluated the feasibility of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy in patients with peripheral T cell lymphomas (PTCLs). PATIENTS AND METHODS: Twenty-six patients with newly diagnosed PTCLs were enrolled into the pilot study. Treatment consisted of classical CHOP plus etoposide 100 mg/m(2) intravenously (i.v.) on day 1 and gemcitabine 600 mg/m(2) i.v. on day 1 in a 3 week interval. RESULTS: Fifteen complete responses (CR, 57.7%) or one unconfirmed complete response (uCR, 3.8%) and four partial responses (PR, 15.4%) were confirmed, giving an overall response rate of 76.9% (95% CI, 58.3-96.3%). Median survival has not yet been reached, while median event free survival was 215 days at a median follow-up duration of 383 days. Estimated overall survival at 1 year was 69.6%. The most severe haematological adverse event was neutropaenia, which occurred with a grade 4 intensity in 14 patients (53.8%). Additionally, febrile neutropaenia was observed in four patients (15.4%). However, there was no treatment-related death. CONCLUSION: The CHOP-EG regimen was found to be feasible in patients with PTCLs. For further investigation on the role of gemcitabine in the treatment of PTCLs, a more large scale phase II or phase III study is warranted.

Clinical Significance of p53, P-glycoprotein, and Glutathione S transferase-pi in Advanced Non-Small Cell Lung Cancer.

PURPOSE: A retrospective study was performed o define the clninical significance of p53, P-glycoprotein (Pgp), and Glutathione S transferase-pi (GST-pi) immunohistochemical (IHC) expression in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reviewed fifty seven patients with advanced NSCLC who had undergone surgical resection or bronchoscopic biopsy between March 1997 and March 1999. IHC staining for p53, GST-pi, and Pgp was performed using formalin-fixed, paraffin-embedded specimens of the fifty seven patients. RESULTS: The IHC expression rate was 63% for p53, 28% for Pgp, and 53% for GST-pi, respectively. The median survival of the fifty seven patients was 45 weeks and the response rate was 38.6% (partial response, 22/57). The chemotherapy response and median survival of the p53 negative group (57% and 61 weeks) were better than those demonstrated by the p53 positive group (28% and 21 weeks) (p<0.05). Additionally, the GST-pi negative group showed a greater improvement of survival and response rate than the positive group (p<0.05). Pgp expression status appeared to have no significant differential effect on chemotherapy response and survival. CONCLUSION: These results suggest that immunohisto chemical staining of p53 and GST-pi may be useful in predicting the response to chemotherapy as well as survival in advanced NSCLC. However, this study is limited by its retrospective nature and the small numbers of tumors studied from a heterogenous group of patients.