Effects of concomitant use of doxifluridine, radiotherapy and immunotherapy in patients with advanced cervical cancer

Clinical effects of doxifluridine (group A, 600 mg/body/day; group B, 800 mg/body/day) combined with radiotherapy and immunotherapy were evaluated in patients with advanced cancer of the uterine cervix. Response rates were 84.2% (16/19 patients) in group A and 100% (18/18 patients) in group B, respectively (p=0.230). There was no significant difference in adverse reaction incidence between the methods but significantly higher grade adverse reaction were observed in group B than in group A (p=0.048). Time to progression (TTP) was longer in group B than in group A (p=0.081). The optimal 5'-DFUR dose was 800 mg/body (group B), by which higher grade adverse reactions were fully controlled and TTP was prolonged.     

免疫治疗联合放疗治疗晚期非小细胞肺癌的进展

晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者手术、放疗、化疗治疗效果欠佳,预后较差。近年来针对NSCLC免疫治疗联合放疗的研究越来越多,可取得较好的肿瘤控制效果。本文就NSCLC免疫治疗联合放射治疗的相关进展进行综述。     

Combined radiotherapy, chemotherapy, and maltose tetrapalmitate immunotherapy in the treatment of 4'dimethylaminoazobenzene-induced liver cancer

Therapeutic effects of radiotherapy (R), chemotherapy, and maltose tetrapalmitate (MTP) immunotherapy alone and in combinations were tried against 4' dimethylaminoazobenzene (DAB) induced primary liver cancer in Wistar rats in three separate protocols. Rats were fed a low protein synthetic diet containing 0.06% DAB for 90-120 days. Around 90 days, liver cancers developed in all the animals. In the first protocol, animals were either left untreated or treated with cyclophosphamide (Cy), MTP (i.p. or oral) and Cy plus oral MTP. Rats in the MTP (i.p.) group maintained a steady liver weight but neither Cy nor Cy + MTP influenced the survival time or liver weight. In the second protocol, R as well as a 3-drug combination at 2 dose levels were tried alone and with MTP before or soon after cessation of DAB feeding. Survival times were decreased by R and chemotherapy due to combined toxicities of DAB and treatments and were partially restored by MTP. In the third protocol, MTP, R, and Cy were each tried alone and in combinations, 21 days after cessation of 100-day DAB feeding. Increase in survivals were obtained by each treatment, although tumor weight was best controlled by triple R+ Cy + MTP combination.     

Influenza vaccination in elderly patients with advanced colorectal cancer.

PURPOSE: To examine influenza vaccination use in patients undergoing chemotherapy for advanced cancer. METHODS: All Medicare patients treated for stage IV colorectal cancer between 1993 and 1998 while living in one of the regions monitored by the Survival, Epidemiology, and End Results Program who were alive in the fall months and who survived at least 4 months with their cancer were considered eligible to have received vaccination. Their medical bills were analyzed to determine receipt of influenza vaccination and subsequent outcomes. RESULTS: Eligibility criteria were met by 1,225 patients who were undergoing chemotherapy during 1,577 person-years of observation. Overall, 39.7% of patients received influenza vaccination, increasing from 26% in 1993 to 43% in 1998. When vaccination was administered, it was provided by primary care physicians 68% of the time. Vaccinated patients were more likely to be white, of higher socioeconomic status, and to have more comorbidity. Fewer diagnoses of influenza and pneumonia infections were made in vaccinated patients while undergoing treatment. Those patients who were immunized also had fewer chemotherapy interruptions and were more likely to survive through to the beginning of the next fall (hazard ratio, 0.88; 95% confidence interval, 0.77 to 0.99). There was a trend toward decreased resource use among immunized patients. CONCLUSION: This study observed outcomes associated with influenza vaccination that are similar to those reported for patients without cancer. However, rates of immunization are relatively low, and disparities exist for vulnerable populations. As part of delivering high-quality care, oncologists should promote influenza vaccination for their patients who are undergoing treatment for advanced cancer.     

Locoregional cellular immunotherapy for patients with advanced esophageal cancer.

The objectives of the present study were to determine the safety of locoregional administration of autologous lymphocytes stimulated with autologous tumor cells and interleukin (IL) 2 in vitro and to find laboratory markers to predict either clinical toxicity or clinical response. Eleven patients with advanced (n = 4) or recurrent (n = 7) esophageal cancers received the locoregional administration of these activated lymphocytes every 2 weeks for two to nine times (mean, 5.6 times), and mean numbers of the administered cells were 0.8 x 10(9) cells per treatment. The activated lymphocytes that were pretested for their surface markers and CTL activity were endoscopically injected into primary tumor sites (n = 4) or directly injected into metastatic lymph nodes (n = 2), pleural (n = 4) or ascitic (n = 1) regions. Grade 3 hypotension, grade 2 diarrhea, and grade 1 fever were observed in 1, 1, and 6 patients, respectively, and there was no adverse effect in the remaining three patients. The clinical outcome was as follows: one, complete response (CR); three, partial response (PR); two, stable response (SR); and five, progressive disease (PD). CTL activity in the administered cells was observed in 5 of the 11 patients (1 CR, 3 PR, and 1 PD) and was not observed in the remaining 6 patients (2 SR and 4 PD). Percentages of CD16+ cells in the peripheral blood of the responder group (CR+PR) significantly increased when compared with those before treatment or with those of the nonresponder group before as well as after treatment. Because the clinical toxicity was moderate and tolerable, this new method of locoregional immunotherapy will be applicable for use in treatment of patients with advanced and recurrent esophageal cancers. Both CTL activity in the administered cells and the percentages of CD16+ cells in the peripheral blood may be useful laboratory markers for predicting of clinical response.     

Local relapse after radiotherapy in locally advanced breast cancer patients

The study includes 99 patients with a locally advanced breast cancer. The mean age was 60.9±12.3 years, and 38.4% of the patients had a T₃ tumors and the remaining patients T₄ lesions. The most common histology was infiltrating ductal carcinoma, and in the 98% of the histologic samples the grade was moderate or high. All patients were treated with modified radical mastectomy, and radiotherapy. 37.4% of the patients received neoadjuvant chemotherapy. The radiotherapy schedule was 50.2%±1.6 Gy (1.8–2 Gy/day) with 1.25 MeV photons. Median follow-up is 4 years. The 5-year local-regional control probability, disease free survival and the distant disease free survival are 96.5%±3.9%, 61.4%±12.3% and 62.1%±12.3% respectively. The 4-year overall survival for patients with T₃ tumors was better than for T₄ lesions (85.8%±11.5% vs 68.5±13.1%) (p=0.18). In conclusion, the management of locally advanced breast cancer, should include surgery, radiotherapy and chemotherapy. The local control was excellent, and although patients die because distant disease they improve ed showed an survival.     

Combined chemotherapy and elemental diet in advanced lung cancer patients

The nutritional and immune status were studied in advanced lung cancer patients receiving combined chemotherapy and an elemental diet to test the effectiveness of the latter. Parameters such as skin tests, lymphocyte count, total protein and albumin values, body weight, and nitrogen balance were improved or maintained by the administration of the elemental diet. A better response to chemotherapy was achieved in patients receiving the elemental diet. Elemental diet support is suggested as a useful addition to chemotherapy in advanced lung cancer.     

益气活血方配合放疗及介入化疗治疗晚期非小细胞肺癌的临床研究

目的探讨益气活血方（YXR）在晚期非小细胞肺癌（NSCLC）治疗中的作用。方法60例NSCLC患者随机分成两组：治疗（A）组：放疗并介入化疗同时用YXR。对照（B）组：放疗并介人化疗。结果两组近期有效率分别为86．7％、76．7％,A、B两组中位生存期、平均缓解期、1年生存率和骨髓抑制率分别为11个月、7．2个月、6．6个月、4个月、60％、33．3％、63％和36.7％。差异有显著性（P＜0．05）。机体免疫力A组治疗后提高,B组降低。结论YXR能提高机体免疫力,减轻骨髓抑制,延长生存期,明显改善生存质量。     

Induced hypertension chemotherapy combined with radiotherapy in 44 advanced cancer patients

This report presents the results of induced hypertension chemotherapy combined with radiotherapy for 44 advanced cancer patients (involving locoregional and/or remote recurrences). The lesions were 16 breast cancers, five soft tissue sarcomas, four lung cancers, four malignant lymphomas, three uterine cancers, two tongue cancers, and one parotid gland cancer, soft palate cancer, malignant thymoma, pancreatic cancer, vaginal cancer, urinary bladder cancer and rectal cancer each. The results, ive., eight complete remissions, 20 partial remissions and 16 cases of no change, were almost satisfactory.     

药物选择剂量分割顺序对放疗联合免疫治疗晚期非小细胞肺癌疗效的影响

非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌总数的85％,53％的患者在确诊时即为晚期.近年来,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)在晚期肿瘤治疗中效果显著.放疗在晚期NSCLC主要用于局部姑息治疗.研究显示免疫治疗协同放疗治...     

Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer

OBJECTIVES: This study evaluated the clinical activity and toxicity of combination chemotherapy with irinotecan and oxaliplatin in patients with advanced pancreatic cancer that had progressed despite > or =1 course of a gemcitabine-containing regimen. METHODS: Thirty patients with metastatic pancreatic cancer and Karnofsky performance status > or =70 received oxaliplatin 60 mg/m2 on days 1 + 15 and irinotecan 60 mg/m2 on days 1 + 8 + 15 every 4 weeks. Patients were assessed on the basis of clinical benefit response, changes in serum tumour marker CA 19-9, objective tumour response, time to progressive disease (TTP), and survival. RESULTS: Six patients (20%) had clinical benefit response (median duration of 7.2 months). CA 19-9 levels were reduced > or =50% from baseline in 8 patients (26%) and remained stable in 8 patients. CT scans revealed that 3 patients (10%) had a partial response and 7 (23%) had stable disease. Two patients (7%) were down-staged and underwent surgery. Median TTP was 4.1 months, median survival was 5.9 months and the 1-year survival rate was 23.3%. The most serious adverse events were grade 3-4 leukopenia in 2 patients (6%), grade 3 neuropathy in 2 (6%) and grade 3 diarrhoea in 1 (3%). CONCLUSION: Chemotherapy with irinotecan and oxaliplatin is an active and well-tolerated combination in patients with advanced pre-treated pancreatic cancer.     

39例晚期胰腺癌立体定向适形放疗的疗效观察

目的探讨立体定向适形放射治疗晚期胰腺癌的疗效。方法39例晚期胰腺癌患者（Ⅲ期30例，Ⅳ期9例），采用立体定向适形放疗技术，每次照射4～5Gy，9～13次完成（隔日1次），总剂量平均为45Gy（36-52Gy）。结果治疗结束后，上腹及腰背部疼痛完全缓解者11例（36．7％），部分缓解17例（56．7％），2例无明显缓解；CR12例（30．8％），PR16例（41．O％），71．8％（28／39）的病例病灶明显缩小；中位生存期11．4月，1年累计生存率为19．2％（5／26）。生存最长者达18个月。结论立体定向适形放射治疗晚期胰腺癌，能改善患者生存质量，延长生存期。     

Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic T lymphocytes

BACKGROUND AND OBJECTIVES: We evaluated the clinical efficacy of adoptive immunotherapy using in vitro activated cytotoxic T lymphocytes (CTL) in the treatment of patients with advanced cancer. METHODS: CTL were induced with the mixed lymphocyte and tumor cell culture method, in which lymphocytes isolated from patient peripheral blood mononuclear cells were mixed with inactivated autologous tumor cells. Activated lymphocytes were administered intravenously to 11 patients once every 2 weeks for 10 weeks (i.e., 5 doses). RESULTS: Tumor reduction and decreased tumor marker were observed in 4 patients. Notably, successful CTL induction was identified in all of these patients. In patients who did not show induction of CTL response, a decreased proportion of lymphocytes, especially CD8(+) cells, and increased levels of CD14(+) cells were frequently observed. Fluorescence-activated cell sorter analysis indicated that expression of HLA class I and costimulatory factor B7-1 molecules was diminished on tumor cells. This was partly recovered with interferon-gamma, which resulted in successful induction of a CTL response. CONCLUSIONS: It was suggested that in vitro CTL induction is difficult in patients with advanced cancer. However, once the cells were induced successfully, some favorable clinical effects were seen by the adoptive transfer of such cell populations.     

Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic,castration-resistant prostate cancer

Purpose

We conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms.

Experimental design

Twenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 10⁷ dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis.

Results

No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13–0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17–0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS.

Conclusions

In patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.     

放疗联合免疫治疗癌症的研究进展

放疗不仅是肿瘤局部治疗的重要手段,同时也对免疫功能有重要的调节作用。放疗可通过产生新抗原、调节细胞因子释放、提高肿瘤对免疫细胞杀伤作用敏感性等方式调节机体抗肿瘤免疫应答。近年来部分研究和临床实践发现,放疗联合免疫治疗在部分病例中出现“远位效应”,照射野范围外的转移性病灶有部分或完全缓解,显示放疗联合免疫治疗的良好前景;但相关机制以及放疗剂量、分割方式等因素对免疫的影响仍有待进一步研究。本文综述了放疗影响免疫的机制以及放疗联合免疫治疗的研究进展。     

Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study

The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m² and the 5FU dosage 150 mg/m²/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m², 5FU 225 mg/m²/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m²) combined with 5FU continuous infusion (225 mg/m²) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.     

热放化疗治疗中晚期宫颈癌近期疗效

目的:探讨盆腹腔深部热疗联合同步放化疗治疗中晚期宫颈癌的疗效和安全性。方法:对2007年2月至2010年10月102例中晚期宫颈癌患者随机分成热放化疗组50例(治疗组)及放化疗组52例(对照组),两组在同样放化疗基础上,治疗组于化疗当天行盆腹腔深部热疗,每次60min,1次/周,共6次。结果:治疗结束后治疗组CR 32例,PR 10例,总有效率84.0%;对照组CR 20例,PR 12例,总有效率61.5%;两组差异有统计学意义(P<0.05)。治疗结束后1个月,治疗组CR 39例,PR 8例,总有效率94.0%;对照组CR 28例,PR 10例,总有效率73.1%;两组差异有统计学意义(P<0.05)。治疗结束3个月时,两组的有效率分别是96.0%、78.8%,两组差异有统计学意义(P<0.01)。两组均有骨髓抑制和消化道反应,经治疗后均可耐受。结论:盆腹腔深部热疗联合同步放化疗可显著提高中晚期宫颈癌患者的近期疗效,早期毒副反应并无增加。     

放疗与免疫治疗联合应用的相关机制及研究进展

放疗主要通过对放射野内肿瘤细胞的杀伤来提高肿瘤的局部控制、降低远处播散并能够激活机体抗肿瘤免疫应答,在免疫治疗的辅助下发挥全身抗肿瘤的作用。放疗联合免疫治疗作为一种新的治疗方式在部分转移性癌症患者中取得了显著疗效。在放射线杀伤局部肿瘤细胞的过程中,肿瘤相关抗原释放表达增加、肿瘤免疫抑制微环境得到改善、激活特异性T细胞免疫应答促使肿瘤细胞形成原位疫苗,合适的放疗剂量与分割模式在最佳时机联合相应的免疫治疗可杀伤放疗野外的远处转移病灶。本文对放疗促进抗肿瘤免疫反应的具体机制以及两者联合应用的广阔前景和面临的挑战进行综述。      

UFTM联合治疗晚期胃癌140例分析

140 patients with advanced gastric cancer confirmed by pathology were treated by UFT (Uracil, FT-207) and mitomycin C (MMC) from Sept. 1985 to June 1987. All the patients received UFT #3 T. i. d. to a total dose of 30 g. Mitomycin C, 8-20 mg i. v. Q. wk was given to a total dose of 48-60 mg. Of the 140 patients, 65 had cancer of cardia, 36 cancer of gastric body, and 39 cancer of gastric antrum. There were 125 males and 15 females. The ages ranged from 30 to 80 years. In this series, CR was 10.0% and PR 44.3% with total remission rate of 54.3% (76/140). Thirty-four patients receiving UFT alone as control had a response rate of 26.5%. The response rate was higher in patients treated with UFTM than those with UFT alone. The median remission was 4 months. That main side effects were leukopenia and thrombocytopenia. The results showed that combination chemotherapy (UFTM) was valid in treating advanced gastric cancer.