Emerging immunological strategies: recent advances and future directions / 医学前沿

Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial / 癌症

The efficacy and safety of bevacizumab with modified irinotecan, leucovorin bolus, and 5-fluorouracil intravenous infusion (mIFL) in the first-line treatment of metastatic colorectal cancer (mCRC) has not been well evaluated in randomized clinical trials in Chinese patients. We conducted a phrase III trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan (125 mg/m(2)), leucovorin (20 mg/m(2)) bolus, and 5-fluorouracil intravenous infusion (500 mg/m(2)) weekly for four weeks every six weeks] plus bevacizumab (5 mg/kg every two weeks) group and the mIFL group, respectively. Co-primary objectives were progression-free survival (PFS) and 6-month PFS rate. In total, 214 patients were enrolled. Our results showed that addition of bevacizumab to mIFL significantly improved median PFS (4.2 months in the mIFL group vs. 8.3 months in the bevacizumab plus mIFL group, P < 0.001), 6-month PFS rate (25.0% vs. 62.6%, P < 0.001), median overall survival (13.4 months vs. 18.7 months, P = 0.014), and response rate (17% vs. 35%, P = 0.013). Grades 3 and 4 adverse events included diarrhea (21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia (19% in the mIFL group and 33% in the bevacizumab plus mIFL group). No wound-healing complications or congestive heart failure occurred. Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC. Clinical benefit and safety profiles were consistent with those observed in pivotal phase III trials with mainly Caucasian patients.

Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the efficacy and safety of cetuximab combined with chemotherapy for patients with advanced colorectal cancer (ACRC) and unclear K-ras status.</p><p><b>METHODS</b>Clinical data of 102 ACRC patients, treated by cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to December 2008, were collected. The cumulative survival rate, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) of the cases were calculated. The difference in ORR, DCR, PFS and oval survival (OS) between the regimens used as first-line and non-first-line treatment, and between the regimens including oxaliplatin and irinotecan were compared.</p><p><b>RESULTS</b>The overall ORR of cetuximab plus chemotherapy was 43.1%, DCR 73.5%, median PFS 4.0 months, OS 28.5 months, and the 1-year, 3-year, and 5-year survival rate was 89.2%, 50.9% and 27.5%, respectively. The differences in ORR (50.0% vs. 40.0%, P = 0.344), DCR (78.1% vs. 72.9%, P = 0.571) and OS (51.0 months vs. 35.0 months, P = 0.396) between the regimens as first line and as non-first line treatment were not statistically significant. However, the PFS of the regimen as first-line was longer than that as non-first-line treatment (PFS 5.5 months vs. 3.0 months, P = 0.001). The differences in ORR (54.2% vs. 40.0%, P = 0.223), DCR (79.2% vs. 74.7%, P = 0.654), PFS (5.0 months vs. 3.0 months, P = 0.726) and OS (36.0 months vs. 40.0 months, P = 0.759) between cetuximab plus oxliplatin and irinotecan were not statistically significant. The most common side effects of cetuximab plus chemotherapy were acneiform eruption (80.4%, grade 3-4 in 9.8%), neutropenia (66.7%, grade 3-4 in 18.6%), and diarrhea (19.6%, grade 3-4 in 5.9%). No treatment-related death was recorded.</p><p><b>CONCLUSION</b>Patients with advanced colorectal cancer and unclear K-ras treated by cetuximab combined with chemotherapy have good ORR and OS, and the regimen is safe with less adverse events for them. There is no significant difference between the efficacies of regimens as first line and as non-first line treatment, and between cetuximab plus oxliplatin and cetuximab plus irinotecan regimens.</p>

Clinical features of hypersensitivity reactions to oxaliplatin among Chinese colorectal cancer patients / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Oxaliplatin is one of the effective drugs for the treatment of advanced colorectal cancer (CRC). Oxaliplatin-induced allergic reactions in European and American patients have been reported, but in China there are only a few case reports. This study investigated the incidence rate and characteristics of oxaliplatin-induced allergic reactions in Chinese patients with CRC.</p><p><b>METHODS</b>Clinical data of 109 patients with advanced CRC receiving oxaliplatin plus capecitabine (the XELOX regimen) as first-line therapy were collected and analyzed retrospectively.</p><p><b>RESULTS</b>Of 109 patients, 13 (11.9%) patients had hypersensitivity. In 546 cycles, 23 (4.2%) cycles involved hypersensitivity. Grade-I,-II, and -III reactions were seen in 13 cycles, 8 cycles, and 2 cycles, respectively, and no grade-IV reaction was observed. Allergic reactions usually occurred at the median time during the fifth cycle (range, the 1st-8th cycle) of oxaliplatin-containing therapy, and the cumulative oxaliplatin dose was 1200 mg (range, 400-1600 mg). Symptoms associated with anaphylaxis appeared 5-360 min (median, 180 min) after oxaliplatin infusion, and were relieved after withdrawing the oxaliplatin infusion and treating with antiallergic drugs. A total of 8 patients continued to receive oxaliplatin therapy after prophylactic administration of antiallergic drugs, such as steroids, and 4 patients did not report persistent allergic reactions. Compared with men, oxaliplatin-induced allergic reactions were more commonly seen in women patients (P<0.05), while age, body surface area, performance status, tumor location, and pathologic type showed no significant difference.</p><p><b>CONCLUSION</b>Oxaliplatin-induced allergic reactions occurred in Chinese patients with CRC, and the incidence rate, occurrence time, degree of severity, and clinical outcome were consistent with literature published abroad.</p>

The expression of hepatitis B virus surface antigen in 120 Hodgkin's lymphoma patients / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Little is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient.</p><p><b>METHODS</b>Clinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen University Cancer Center between January 2004 and October 2007 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis.</p><p><b>RESULTS</b>Of the 120 patients, 18 (15.0%) were hepatitis B virus surface antigen HBsAg-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (I + II) and advanced-stage (III + IV) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P < 0.001), while not significantly different in advanced-stage group (75.0% vs. 84.8%, P = 0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P = 0.006 and 0.014, respectively).</p><p><b>CONCLUSIONS</b>The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.</p>

Efficacy and prognostic analysis on surgical resection of pulmonary metastasis from colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To elucidate the efficacy and probable prognostic factors of surgical resection of pulmonary metastasis from colorectal cancer.</p><p><b>METHODS</b>Clinical data and outcomes of 35 colorectal patients with pulmonary metastasis undergone pulmonary metastasectomy were analyzed retrospectively.</p><p><b>RESULTS</b>Median follow-up time was 48.0 months. The median overall survival time was 36.0 months. Five-year survival rate was 33.0%. Nineteen patients died of tumor progression. Sixteen patients were survival including survival with tumor (10 cases) and without tumor (6 cases). One patient was still alive without tumor for 164 months. Univariate analysis revealed that disease free interval (DFI) was a prognostic risk factor, while gender, age, primary tumor site, pulmonary metastasis size and location, surgical procedure, pre-surgical CEA level, re-metastasectomy did not show influence on the survival time after pulmonary metastasectomy.</p><p><b>CONCLUSIONS</b>For some selected patients with indication, pulmonary metastasectomy may be a potential curative method. DFI may be associated with the prognosis after pulmonary metastasectomy.</p>

CEOP regimen in the treatment for non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study is to analyse the efficacy and toxicity of CEOP regimen in the treatment of non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>From January 1995 to December 2000, 121 patients with NHL were treated by CEOP regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analysed retrospectively.</p><p><b>RESULTS</b>Of these 121 patients, 83 (68.6%) had B-cell NHL and 38(31.4%) peripheral T or NK-cell NHL; 55. 4% (67/121) had early disease (stage I or II), and 89.3% (108/121) had IPI score 0-2. The median age was 53 years (range: 7-79 yr). All patients were treated by CEOP regimen (totally, 471 cycles) with or without radiotherapy. The overall response (OR) rate in this series was 90.9% (110/121) with a complete remission (CR) rate of 71.9% (87/121); whereas the response rate of chemotherapy alone was 88.4% (107/121) with a CR rate of 67.8% (82/121). Major toxicity consisted of grade III-IV myelosuppression (11.9%), neutropenia (1.9%) and thrombocytopenia and anemia (1.1%). Alopecia was observed in 46.3%. However, cardiotoxicity was mild and reversible. Median follow-up duration in this series was 63 months (range: 2-116 months). The overall 1-, 3- and 5-year survival rate was 84.8%, 62.7% and 55.9%, respectively, with a median survival time of 85 months (2-118 months).</p><p><b>CONCLUSION</b>Our data show that CEOP regimen combined with or without radiotherapy for the involved field is effective and well tolerated by the patients with non-Hodgkin's lymphoma.</p>