Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer

This study aimed to evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy intensified with irinotecan in patients with locally advanced rectal cancer. Eligible patients had nonmetastatic disease at a locally advanced stage that made R0 resection and sphincter preservation uncertain. They received preoperative radiation over 6 weeks to 45 Gy and boost of 5.4 Gy and concurrent continuous infusion 5-fluorouracil 250 mg m(-2) day(-1) and weekly irinotecan 40 mg m(-2). In all, 37 patients entered the study. T stage at baseline as determined by ultrasound was T2/T3/T4 in 2/19/16 patients; 31 patients had lymph node involvement. The predominant toxicity was diarrhoea (grade 3/4 in 10/2 patients). Haematologic toxicity and surgical complications were moderate. Among 36 patients undergoing surgery, 32 (89%) had R0 resection and 23 (64%) sphincter preservation. Pathologic complete response (pCR) was achieved in eight (22%) of 36 patients, and 10 patients (28%) had only microscopic residual disease. At 4 years, overall survival was 66%, disease-free survival 73%, local relapse rate 7%, and distant failure rate 24%. Extent of resection and postoperative nodal status were significant predictors of overall and disease-free survival. Intensified neoadjuvant chemoradiotherapy with irinotecan can be safely administered and results in a high pCR rate.     

四种辅助治疗方案联合手术对中晚期食管癌疗效的对比研究

[目的]分析辅助治疗对中晚期食管癌的临床价值。[方法]230例中晚期食管癌（T2-4NXMO）患者,按照治疗方法分成4组,NRT组予术前放疗,NCRT组予术前放化疗,PRT组予术后放疗,PCRT组予术后放化疗,分析4组复发率、5年生存率。[结果]NRT、NCRT、PRT、PCRT组1年局部复发率分别为72.8%、30.7%、80.1%、35.6%,差异有显著性（χ2=4.159,P=0.000）;5年生存率分别为8.82%、33.33%、14.28%和19.18%,差异有显著性（χ2=13.812,P=0.003）。[结论]术前放化疗治疗中晚期食管癌可降低局部复发率,并提高远期生存率。     

食管癌的新辅助治疗进展

新辅助治疗是在成功的术后辅助治疗经验基础上提出的术前辅助治疗。其目的是增加手术切除肿瘤的可能性并提高患者的生存率,包括新辅助化疗、新辅助放疗和新辅助放化疗。本文拟就食管癌的新辅助治疗作一综述。     

直肠癌的新辅助治疗

为了保留肛门、减少复发、延长生存,新辅助化放疗已成为直肠癌治疗的重要组成部分.本文详细论述了直肠癌新辅助治疗的发展和现状.探讨了新辅助放疗、新辅助放化疗与单纯手术及辅助化放疗相比的优劣.     

Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer

Background: Neoadjuvant chemotherapy is increasingly being used for the treatment of bulky and locally-advanced cervical cancer. Cisplatin and ifosfamide are known to be effective in cervical cancer, while paclitaxel is one of the promising new drugs for the treatment of this neoplasm.Objective: To assess the toxic effects and antitumor activity of a multidrug neoadjuvant regimen consisting of cisplatin, ifosfamide, and paclitaxel in bulky and locally advanced cervical cancer.Patients and methods: Thirty-eight patients with pathology-confirmed squamous-cell cervical cancer (27 IB2-IIA, two IIB, eight IIIB, one IVA) were prospectively enrolled in the study. Their treatment consisted of paclitaxel 175 mg/m² given over three hours on day 1, cisplatin 50 mg/m² (75 mg/m² in 10 patients), ifosfamide 5 g/m² in a 24-hour continuous infusion and mesna 5 g/m² in a 24-hour continuous infusion on day 2, and mesna 3 g/m² in a 24-hour continuous infusion on day 3. The course was repeated every three weeks for three courses and all of the patients, except those with disease progression or who were inoperable, were scheduled for radical hysterectomy and pelvic lymphadenectomy.Results: All patients are evaluable for response. Eleven achieved clinical complete responses, 21 had partial responses, five had stable disease and one had progression of disease. Of 34 patients who underwent surgery, six (16%) had pathology-documented complete responses, seven (18%) had partial responses with only microscopic residual disease in the cervix, 19 had sub-optimal partial responses, and two had stable disease, for an overall response rate of 84% (95% confidence intervals (CI): 68.7%–94%).Grade 3–4 neutropenia was recorded for 27 (71%) patients, grade 3–4 thrombocytopenia for four (10.5%), and grade 2 peripheral neuropathy for two (2.5%).At a median follow-up of 16 months (range 7–22), 29 (76%) women are alive without recurrence, seven are alive with persistent/recurrent disease and two have died of their disease.Conclusions: According to pathology examination, this regimen yields a 34% complete and optimal partial response rate with acceptable toxicity, and it should be prospectively compared to other regimens.     

Neoadjuvant Therapy with Drug Arglabin for Breast Cancer with Expression of H-Ras Oncoproteins

Backgrounds: In breast cancer, blocking of Ras signaling and inhibition of H-Ras is quite promising. H-Ras may become a target for farnesyl transferase inhibitors, and in combination with other immunohistochemical factors it will contribute to the progression of a breast tumor. Purpose: The aim of this study was to evaluate the effectiveness of neoadjuvant therapy for breast cancer with the inclusion of farnesyl transferase inhibitor, arglabin interfering with the expression and concentration of H-Ras oncoproteins. Methods: Depending on the presence of H-Ras oncoproteins after Western-blot hybridization, the patients were divided a negative and positive expression of H-Ras groups. Results: Correlation analysis of methods used for determining the expression ability and concentration of H-Ras oncoproteins (immunohistochemistry and Western-blot analysis) demonstrated substantial statistical relationship Rs=0.71, p=0.03. The H-Ras oncoproteins were absent in patients receiving either “Arglabin” or standard AC regimen. However, in the AC + Arglabin group, there was a varying degrees of positive concentration of H-Ras oncoproteins (Kruskal-Wallis=6.92; p=0.03). Conclusion: These results indicate that Arglabin attenuates H-Ras oncoproteins expression which is a promising therapeutic target for breast cancer.     

35例局部晚期胃癌EOLF方案新辅助化疗临床观察

[目的]探讨局部晚期胃癌新辅助化疗的治疗效果。[方法]35例局部晚期胃癌采用EOLF方案(CF 5-Fu LOHP E-ADM)术前化疗,1～2个周期后重新分期、评价疗效并手术。[结果]35例患者中,无临床完全缓解病例,部分缓解(PR)19例,稳定(SD)9例和进展(PD)7例;临床降期19例,化疗后手术切除率达91.3%。[结论]新辅助化疗可以降低部分局部晚期胃癌的临床分期,提高手术切除率。     

Influence of Adriamycin Dose in the Outcome of Patients with Osteosarcoma Treated with Multidrug Neoadjuvant Chemotherapy: Results of Two Sequential Studies

Summary

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m² instead of 360 mg/m²) or the single dose per cycle of this drug (60 mg/m² instead of 90 mg/m²) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol – in comparison with the first protocol – after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51 – 73% vs 123/144 – 85%: P < 0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.     

术前应用FOLFOX方案联合放疗治疗中低位直肠癌35例报告

目的探讨术前应用FOLFOX4方案化疗联合放疗治疗中低位局部进展期直肠癌的安全性和有效性。方法对本院2006年3月以来35例术前应用FOLFOX4方案联合放疗进行新辅助治疗的中低位局部进展期直肠癌患者资料进行分析。结果低位前切除术20例,腹会阴联合切除15例,保肛率为57．1％（20／35）。30例患者（85．7％）新辅助治疗后排便困难、便次增多、便血等症状得以改善。肿瘤完全消退5例,肿瘤部分缓解26例,病情稳定4例,治疗有效率为88．6％（31／35）。病理完全缓解率为14．3％;肿瘤分期降低25例,降期率为71．4％。结论FOLFOX4术前化疗方案应用于中低位局部进展期直肠癌的新辅助治疗安全有效,可达到大部分患者术前肿瘤降期。     

食管癌的新辅助化疗和辅助化疗现状

食管癌是我国最常见的恶性肿瘤之一,严重威胁着人们的健康和生命。早期食管癌的治疗首选手术。为了提高局部晚期食管癌的疗效,人们进行了多种治疗模式的探索,如术前放疗、术前化疗、术前放化疗以及术后化疗等。本文就目前新辅助化疗和辅助化疗在食管癌治疗中的价值作一综述。     

Neoadjuvant docetaxel followed by adjuvant doxorubicin and cyclophosphamide in patients with stage III breast cancer.

BACKGROUND: To evaluate clinical and pathologic response to neoadjuvant docetaxel therapy in patients with stage III breast cancer. Patients and methods: Forty-five patients were planned to receive four cycles of docetaxel 100 mg/m2 every 3 weeks, followed by surgery, four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) every 3 weeks, radiation therapy (RT), and tamoxifen when indicated. RESULTS: After four cycles of neoadjuvant docetaxel, the clinical response rate within the breast was 59% (95% CI 42% to 73%) and overall (breast and axilla) was 49% (95% CI 38% to 72%) in the intention-to-treat (ITT) population. At the time of surgery, 10% (n=4) of patients had a pathologic complete response (pCR) in the breast, 27% (n=11) had a pCR within the axillary lymph nodes, and 7% (n=3) had a pCR in the breast and axilla (95% CI 2% to 21%). An additional 5% (n=2) had minimal residual invasive tumor (<5 mm). The 5-year overall survival rate was 80%. The percentage of patients with grade 3/4 neutropenia was similar during docetaxel (93%) and AC (86%), while a greater percentage of patients had febrile neutropenia during docetaxel treatment (27%) compared with AC treatment (7%). CONCLUSIONS: Neoadjuvant docetaxel followed by surgery, adjuvant AC, hormonal therapy where indicated, and RT is an active regimen for patients with stage III breast cancer.     

Lack of pathologic down‐staging with neoadjuvant chemotherapy for muscle‐invasive urothelial carcinoma of the bladder

BACKGROUND:

The postcystectomy survival benefit associated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) neoadjuvant chemotherapy (NC) for muscle‐invasive bladder cancer has been most evident in patients who achieve a pathologic complete response. The outcome of NC and open radical cystectomy (RC) was evaluated in a contemporary cohort of patients in a tertiary referral setting.

METHODS:

From January 2006 to November 2007, 117 patients underwent open RC at Cleveland Clinic for muscle‐invasive bladder cancer, 29 (25%) of whom received NC. Patient information was obtained from a prospective database.

RESULTS:

Clinical stage at the time of diagnosis in the NC cohort was T2 in 23 (79%) and T3‐4a in 6 (21%) patients. A total of 20 (69%) patients received the combination of gemcitabine and cisplatin (GC), 4 (14%) received MVAC, and 5 (17%) received other regimens. The median interval from the time of diagnosis of muscle‐invasive bladder cancer to RC was 208 days (interquartile range, 149 days ‐327 days) in the NC cohort. Overall, only 2 patients (7%; 95% confidence interval [95% CI], 0 patients‐17 patients) achieved a pathologic complete response, 18 (62%; 95% CI, 43 patients‐81 patients) had nonorgan‐confined residual cancer, and the overall median progression‐free survival was 10.5 months (95% CI, 7 months ‐14 months).

CONCLUSIONS:

Few RC patients in these investigators' recent experience achieved a pathologic complete response with NC, and most experienced rapid disease progression. These poor outcomes may be related to the use of non‐MVAC‐based regimens or excessive delay in performing RC. In the absence of supportive data for GC in the neoadjuvant setting, MVAC remained the preferred regimen. Excessive delays in performing RC may negate the benefit of NC. Cancer 2009. © 2009 American Cancer Society.     

Efficacy and safety of neoadjuvant trastuzumab combined with paclitaxel and epirubicin: a retrospective review of the M. D. Anderson experience

BACKGROUND: A previously published prospective randomized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy (PST) with paclitaxel and FEC(75) (fluorouracil, epirubicin, cyclophosphamide) concurrently with trastuzumab in patients with HER2-positive primary breast cancer resulted in a 60% pathologic complete response rate (PCR) with no associated severe cardiac toxicity. The purpose of this study was to review the efficacy and safety of a similar regimen outside the setting of a clinical trial. METHODS: Patients with HER2-positive breast cancer (defined as either immunohistochemical 3+ or fluorescence in situ hybridization-positive) that had received 24 weeks of neoadjuvant trastuzumab concurrently with taxane and anthracycline-based chemotherapy between 2004 and 2006 were included in the analysis. PST chemotherapy consisted of paclitaxel (80 mg/m(2)) weekly for 12 weeks followed by 4 cycles of FEC(75) (500 mg/m(2), 75 mg/m(2), and 500 mg/m(2), respectively). RESULTS: Forty patients were identified. The median age was 48 years (range, 29-81). In all, 60% of patients had stage III disease and 4 had inflammatory breast cancer. The PCR rate was 55% (95% confidence interval [CI], 38.5%-70.7%). At a median follow-up of 19 months. 5 patients had a recurrence, of which 4 did not achieve a PCR. No severe cardiac events were observed. CONCLUSIONS: Stage II and III HER2-positive breast cancer patients achieved a high rate of PCR with trastuzumab given concurrently with paclitaxel and FEC(75) chemotherapy. No severe cardiac events were observed with the regimen. The data concur with the results of a previously published trial.     

进展期胃癌的术前新辅助治疗进展

自美国INT0116试验结果发表以后,胃癌术后辅助治疗已经成为局部晚期胃癌的标准治疗方法,但对胃癌术前新辅助治疗的价值,目前还未能达成共识.现临床有大量研究显示:通过术前新辅助治疗,不仅可以提高患者的R0切除率,还可以减少复发转移,提高患者生存期,该文就目前国内外关于进展期胃癌术前新辅助治疗的进展进行综述.     

Prognostic role of EGFR gene copy number and KRAS mutation in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy

Background:

Epidermal growth factor receptor (EGFR), evaluated by immunohistochemistry, has been shown to have prognostic significance in patients with colorectal cancer. Gene copy number (GCN) of EGFR and KRAS status predict response and outcome in patients treated with anti-EGFR therapy, but their prognostic significance in colorectal cancer patients is still unclear.

Methods:

We have retrospectively reviewed the baseline EGFR GCN, KRAS status and clinical outcome of 146 locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiotherapy. Pathological response evaluated by Dworak''s tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS) were analysed.

Results:

Tumour regression grade 4 and TRG3–4 were achieved in 14.4 and 30.8% of the patients respectively. Twenty-nine (19.9%) and 33 patients (19.2%) had an EGFR/nuclei ratio >2.9 and CEP7 polisomy >50% respectively; 28 patients (19.2%) had a KRAS mutation. Neither EGFR GCN nor KRAS status was statistically correlated to TRG. 5-year DFS and OS were 63.3 and 71.5%, respectively, and no significant relation with EGFR GCN or KRAS status was found.

Conclusion:

Our data show that EGFR GCN and KRAS status are not prognostic factors in LARC treated with preoperative chemoradiation.     

中晚期鼻咽癌新辅助化疗联合放疗的临床研究

目的:探讨新辅助化疗联合放疗治疗中晚期鼻咽癌的疗效。方法:自1998年1月至2002年11月,92例中晚期鼻咽癌患者分别采用新辅助化疗联合放疗(化放组)及单纯放疗(单放组)。新辅助化疗组在放疗前给予DDP 5-Fu化疗2周期,二组放疗相同。鼻咽DT(68~72)Gy/(7~7.5)W,颈部50Gy~76Gy/(5~8)W,比较二组疗效及不良反应。结果:放疗结束时鼻咽肿瘤完全退缩率二组分别为60.4%,38.6%(P<0.05),颈部淋巴结完全退缩66.7%,36.4%(P<0.05),急性反应化放组的胃肠道反应,白细胞下降等副反应增加。1年生存率化放组及单放组分别为81.3%,81.8%(P>0.05),3年生存率分别为58.3%,61.3%(P>0.05)。结论:新辅助化疗联合放疗治疗中晚期鼻咽癌能提高近期鼻咽病灶及颈淋巴结完全消退率,未能提高中晚期病人的生存率,未能降低远处转移的几率。