HCPT联合L-OHP方案治疗复发转移结直肠癌的近期临床疗效

背景与目的:虽然含氟尿嘧啶(5-fluarouracil,5-FU)联合方案是目前治疗结直肠癌的标准方案,但是作为二线治疗的疗效不高,探索新的替代方案显得十分必要。本研究拟应用羟基喜树碱(hydroxycampothecin,HCPT)联合草酸铂(oxaliplatin,L-OHP)方案治疗复发转移结直肠癌,并观察其近期疗效、不良反应及1年生存率。方法:47例经病理学检查证实的复发转移结直肠癌,采用HCPT L-OHP方案治疗86个周期,HCPT6mg/m2 NS500ml,静脉滴注d1～4;L-OHP130mg/m2 5%GS500ml,静脉滴注d1。每例治疗2个周期后进行近期临床疗效和不良反应评定,两次化疗间隔为3周。结果:38例可进行疗效评价,总有效率(CR PR)为36.8%(14/38)。化疗后KPS改善和显著改善者20例,占52.6%。白细胞下降59周期,占68.6%,其中Ⅲ～Ⅳ度白细胞下降18周期,占30.5%;腹泻48周期,占55.8%,其中Ⅲ～Ⅳ度腹泻18周期,占37.5%。1年生存率为40.0%,中位总生存期(medianoverallsurvival,mOS)和中位无进展生存期(medianprogressionfreesurvival,mPFS)分别为11.7和7.8个月。结论:HCPT L-OHP方案治疗一线化疗后复发的结直肠癌病例有较好的近期临床疗效,主要不良反应是白细胞下降和腹泻。     

Single-agent capecitabine in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin chemotherapy

OBJECTIVE: The effectiveness of capecitabine, an oral fluoropyrimidine carbamate, is well documented in previously untreated metastatic colorectal cancer patients (overall response rate: 25%). However, its efficacy in patients with metastatic colorectal cancer refractory to 5-fluorouracil/leucovorin (5-FU/LV) has not been determined. This study was performed to evaluate the efficacy and to identify the side-effects of capecitabine in patients with metastatic colorectal cancer showing progression despite 5-FU/LV-based combination chemotherapy. METHODS: Fifty-one metastatic colorectal cancer patients who showed progressive disease in 5-FU/LV-containing regimens (median: two regimes) were treated with capecitabine 1,250 mg/m(2) twice daily (days 1-14 repeated every 3 weeks). RESULTS: Only one partial response was observed (response rate: 2%). Twenty-seven patients (53%) showed stable disease after two cycles. The median time to disease progression of either a partial response or stable disease was 3.4 months. Hand-foot syndrome was the main toxicity of capecitabine and occurred in 35% of cases (grade 3 or 4 in 6%). The median number of cycles administered was two and the relative dose intensity of capecitabine was 80%. CONCLUSION: The response rate to capecitabine was low in metastatic colorectal cancers that were refractory to 5-FU/LV-containing chemotherapy. However, disease stabilization was seen in a significant number of patients.     

HCPT联合L-OHP方案治疗进展期结直肠癌的近期临床疗效

Objective： Although 5-fluarouracil-based chemotherapy has become a standard regimen for treatment of advanced colorectal cancer, the efficacy, as second line therapy, is not high. It is necessary to find a new regimen as a substitute for these patients. The study was to evaluate the short-time effects and toxicity of combination of HCPT plus L-OHP regimen in treatment of advanced colorectal cancer. Methods： Forty-seven patients with pathological evidence of advanced colorectal cancer were enrolled and were treated with HCPT plus L-OHP regimen for 86 cycles. All patients were treated with L-OHP 130 mg/m^2 day 1 and HCPT 6 mg/m^2day 1-4, the chemotherapy was repeated every 3 weeks as a cycle. The Short-time efficats and side effects were evaluated after 2 cycles for each patient. Results： 38 cases can be evaluated to short-time effects and achieved the overall response rate （CR＋PR） was 36.8%. KPS improved in 20 cases （52.6%）. In the total 86 cycles, the leucopenia occurred in 59 cycles （68.6%）,18 cycles （30.5%） in grade Ⅲ and Ⅳ and the diarrhea occurred in 48 cycles （55.8%）, 18 cycles （37.5%） in grade Ⅲ and Ⅳ. Conclusion： A satisfied response rate was obtained in advanced colorectal cancer patients treated by HCPT plus L-OHP regimen, especially who were the failure of first-line chemotherapy with 5-FU. The limited-dose toxicity was leucopenia and diarrhea.     

Phase II study of biweekly irinotecan and mitomycin C combination therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer

PURPOSE: Experimental studies have shown that mitomycin C (MMC) acts synergistically with irinotecan. We evaluated the antitumor activity and toxicity of a combination of irinotecan and MMC in patients with metastatic colorectal cancer resistant to fluoropyrimidines. METHODS: Eligible patients had evidence of tumor progression while receiving fluoropyrimidine-based regimens or had disease recurrence within 6 months after the completion of adjuvant treatment with fluoropyrimidines. Irinotecan (150 mg/m(2)) and MMC (5 mg/m(2)) were administered on days 1 and 15 of a 28-day cycle. Treatment was repeated every 4 weeks. RESULTS: Among the 41 patients enrolled, 37 (90%) had received previous chemotherapy for metastatic disease, and 4 had received adjuvant chemotherapy alone. Objective responses were observed in 14 patients (34%, 95% confidence interval 20-49%). The median time to progression was 4.2 months, and the median survival time was 11.9 months. The study treatment was well tolerated; the median number of cycles received was four. Grade 3 or 4 neutropenia, the most common toxic effect, occurred in 20 patients (49%). Grade 3 or 4 thrombocytopenia occurred in four patients (10%) and grade 3 diarrhea in one patient. CONCLUSIONS: Our results suggest that irinotecan and MMC combination therapy is effective and well tolerated in patients with fluoropyrimidine-resistant metastatic colorectal cancer. Further clinical investigation of this regimen is warranted.     

Multicenter phase II study of fractionated bimonthly oxaliplatin with leucovorin and 5-fluorouracil in patients with metastatic colorectal cancer,pre-treated with chemotherapy

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.     

Effect of a 3-hour interval between methotrexate and 5-fluorouracil in the treatment of metastatic colorectal cancer

OBJECTIVE: This phase II study was designed to evaluate the efficacy and toxicity of 3-h interval sequential methotrexate (MTX) and 5-fluorouracil (5-FU) with leucovorin (LV) rescue in the treatment of patients with metastatic colorectal cancer. METHODS: Forty-two patients with histologically confirmed metastatic colorectal cancer and at least one two-dimensionally measurable lesion, aged 30-74 years old, with performance status < or =2 and no or one prior chemotherapy were selected. Patients received sequential MTX 100 mg/m2 by bolus injection and 5-FU 600 mg/m2 at 3 h followed by LV rescue initiated after 24 h (15 mg per body every 6 h for six doses). The treatment was repeated every week or every 2 weeks until disease progression. All patients were treated as out-patients unless complications arose. RESULTS: All 42 patients entered in this study were assessable both for response and toxicity. Fifteen patients achieved objective responses (one complete and 14 partial), for an overall response rate of 36% (95% CI: 11-51%). Response rates in pretreated patients and patients with naive chemotherapy were 27 and 42%, respectively. Sixteen patients had stable disease and 11 progressed with therapy. The median survival for all patients was 378 days. The hematological toxicity was mild with no grade 3/4 leukopenia. The major non-hematological toxicity was diarrhea (one grade 4, four grade 3). CONCLUSIONS: This 3-h interval sequential MTX and 5-FU with LV rescue is an active regimen in patients with metastatic colorectal cancer. The treatment showed mild toxicity and was administered on an out-patient basis. The present findings suggest that this regimen warrants further investigation in patients with metastatic colorectal cancer.     

奥沙利铂联合氟尿嘧啶及甲酰四氢叶酸治疗晚期大肠癌近期疗效分析

目的 :评价国产奥沙利铂 (oxaliplatin ,L OHP)联合氟尿嘧啶及甲酰四氢叶酸 (CF)治疗大肠癌的疗效和毒副反应。方法 :2 8例晚期大肠癌患者 ,予国产L OHP 12 0mg/m2 ,静脉滴入 ,持续 2h ;CF 15 0mg/m2 ,静脉滴入 ,持续 2h ;5 -氟尿嘧啶 ( 5 FU ) 5 0 0mg/m2 ,静脉滴入 ,持续 >4h ,于CF滴完后用。每 3周重复 1次 ,用药 2个周期后评价疗效。结果 :2 8例患者中 ,无完全缓解 (CR) ,部分缓解 (PR) 9例 ,稳定 (SD) 12例 ,进展 (PD) 7例 ,总有效率(RR ,CR PR) 3 2 1% ( 9/2 8) ,中位无进展生存期 6 7个月 ,中位生存期 9 8个月。毒副反应主要是末梢神经毒性、恶心呕吐、骨髓抑制及静脉炎等 ,患者均可耐受。结论 :国产L OHP联合 5 FU /CF治疗晚期大肠癌具有较好的疗效     

Combined irinotecan and oxaliplatin plus granulocyte colony-stimulating factor in patients with advanced fluoropyrimidine/leucovorin-pretreated colorectal cancer.

PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted of oxaliplatin 85 mg/m2 on days 1 + 15 and irinotecan 80 mg/m2 on days 1 + 8 + 15 every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of scheduled chemotherapeutic drug administration, a 5-day course of granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d was given. RESULTS: The overall response rate was 42% for all 36 assessable patients (95% confidence interval, 26% to 59%), including two complete remissions (6%). Thirteen additional patients (36%) had stable disease, and only eight (22%) progressed. The median time to treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic toxicity was commonly observed, although according to the ANC-adapted use of G-CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and 4 granulocytopenia occurred in only five and two cases, respectively. The most frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that the combination of irinotecan and oxaliplatin with or without G-CSF has substantial antitumor activity in patients with progressive fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was modest, with gastrointestinal symptoms constituting the dose-limiting side effects. Further evaluation of this regimen seems warranted.     

Phase II trial of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer

BACKGROUND: Both irinotecan and oxaliplatin are active agents in the treatment of patients with metastatic colorectal cancer, and there is a strong preclinical rationale for combining these 2 agents. Therefore, a Phase II trial was designed and conducted to determine the efficacy and tolerability of combined irinotecan and oxaliplatin given every 3 weeks to patients with metastatic colorectal cancer. METHODS: Patients with previously untreated metastatic colorectal cancer received irinotecan at a dose of 175 mg/m2 and oxaliplatin at a dose of 130 mg/m2, both given intravenously every 3 weeks. Objective responses were evaluated every 2 courses and were confirmed at least 4 weeks after the initial determination. RESULTS: Fifty-five patients were enrolled and treated in the current trial. Of the 53 patients whose responses were evaluable, 18 (34%) achieved a partial response, 27 (51%) had stable disease, and 8 (15%) developed disease progression as their best response to the treatment. The intent-to-treat median survival for all patients was 16.4 months and the time to progression was 4.8 months. All 55 patients were available for toxicity analysis (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria). The most common Grade 3-4 toxic effect was neutropenia, which was reported to occur in 22 patients (40%). CONCLUSIONS: The combination of irinotecan and oxaliplatin appears to be safe and active when used to treat patients with metastatic colorectal cancer. Treatment results with this regimen were similar to those reported for other combined frontline chemotherapy regimens for colorectal cancer. When this particular regimen wa used, neutropenia was found to be the predominant toxicity.     

Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer

Aim: There has been limited data on capecitabine monotherapy in metastatic colorectal cancer (CRC) patients who were previously treated with both oxaliplatin/5‐fluorouracil(FU)/leucovorin (FOLFOX) and irinotecan/5‐FU/leucovorin (FOLFIRI). Methods: We analyzed 20 patients between August 2002 and March 2008 with metastatic CRC who had been treated with capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. Results: Overall, one partial response was observed (overall response rate, 5%) and stable disease was observed in 11 patients (55.0%). The disease control rate was 60.0%. The median progression‐free survival (PFS) was 2.3 months (95% CI 1.9–2.7) and the median overall survival (OS) was 5.3 months (95% CI 4.6–6.0). Patients without ascites had longer PFS than those with ascites (P = 0.02). Patients with more than three metastatic sites had poorer OS than those with less than two (P = 0.01). Grade 3 or 4 non‐hematological toxicities included hand–foot syndrome in one patient. There were no grade 3 or 4 hematological toxicities or treatment‐related deaths. Conclusion: The capecitabine monotherapy had a moderate disease control rate and a tolerable toxicity profile as third‐line or fourth‐line treatment for metastatic CRC patients who were refractory to standard chemotherapy with no further treatment options.     

奥沙利铂联合方案区域动脉灌注治疗晚期大肠癌的临床观察

目的观察奥沙利铂(L-OHP)联合甲酰四氢叶酸(CF)和5-氟尿嘧啶(5-Fu)腹腔区域动脉灌注治疗晚期大肠癌的临床效果和毒副反应.方法采用Seldinger方法,23例晚期大肠癌患者根据肿瘤部位不同将导管插入相应主要供血动脉,治疗组11例,动脉灌注L-OHP、CF、5-Fu;对照组12例,动脉灌注顺铂(PDD)、CF、5-Fu.每三周重复一次,治疗二次后评价疗效.结果临床症状缓解率、肿瘤有效率:治疗组为72.7%、63.6%;对照组为41.7%、33.3%;两组有显著性差异(P＜0.05).两组毒副反应主要有恶心、呕吐、腹泻、粘液血便、白细胞下降,大多为Ⅰ～Ⅱ度;对照组发生率较治疗组高,治疗组感觉神经毒性明显升高,但停药后可缓解.结论L-OHP联合CF、5-Fu腹腔区域动脉灌注治疗晚期大肠癌具有疗效好,毒副反应轻、能耐受的特点.     

西妥昔单抗联合放化疗治疗中晚期恶性肿瘤

背景与目的：西妥昔单抗是一种特异性阻断EGFR的单克隆抗体.本研究观察西妥昔单抗联合放化疗治疗晚期头颈部和结直肠癌的有效性和安全性.方法：全组6例患者,均经病理证实,西妥昔单抗联合伊立替康、卡培他滨方案治疗晚期结直肠癌;联合多西他赛、放疗治疗晚期头颈鳞癌.西妥昔单抗首剂400 mg/m2,然后250 mg/m2每周1次维持.结果：6例患者治疗后取得PR 2例,SD 3例,PD 1例,中位TTP 18.5周.其中3例晚期头颈鳞癌患者,PR 1例,SD 2例;3例晚期中分化结直肠癌患者,PR 1例,SD 1例,PD 1例.主要的毒性反应是痤疮样皮疹和腹泻.结论：西妥昔单抗联合多西他赛＋放疗治疗晚期头颈鳞癌,西妥昔单抗联合伊立替康、卡培他滨治疗晚期结直肠癌患者有效.除皮疹之外,毒副反应较单用化疗、放疗无明显增加.     

Efficacy and safety of an irinotecan plus bolus 5-fluorouracil and L-leucovorin regimen for metastatic colorectal cancer in Japanese patients: experience in a single institution in Japan

BACKGROUND: Short-term infusion of 5-fluorouracil with leucovorin in combination with irinotecan or oxaliplatin has been considered as standard treatment for metastatic colorectal cancer. However, until infusion of 5-fluorouracil regimens and oxaliplatin was approved for the treatment of metastatic colorectal cancer in Japan early in 2005, combination of irinotecan with bolus 5-fluorouracil/leucovorin had been the standard treatment. This retrospective study evaluates the efficacy and safety of a modified irinotecan with bolus 5-fluorouracil/leucovorin regimen in Japanese colorectal cancer patients. METHODS: Forty-six patients untreated with chemotherapy for metastatic colorectal cancer received a modified form of the irinotecan with bolus 5-fluorouracil/leucovorin regimen, consisting of intravenous irinotecan (100 mg/m2) and l-leucovorin (10 mg/m2), and then 5-fluorouracil 500 mg/m2 as an intravenous bolus infusion, weekly for 4 weeks, repeated every 6 weeks until progression or unacceptable toxicity. RESULTS: The overall response rate was 48% (95% confidence interval, 34-62%), and 48% of patients had stable disease. Median progression-free survival was 8.3 months and overall survival was 20.3 months. The incidence of grade 3 or 4 toxicity was as follows: neutropenia, 50%; diarrhea, 4%; fatigue, 13%; nausea, 7%; and vomiting, 7%. Neither treatment-related nor all-cause mortality occurred within 60 days of chemotherapy initiation. Despite the limited availability of oxaliplatin, 29 patients received an oxaliplatin-based regimen after progression. CONCLUSION: A modified irinotecan plus bolus 5-fluorouracil/l-leucovorin regimen was an active and well-tolerated regimen in Japanese patients with advanced colorectal cancer, showing a different toxicity profile from Western patients.     

奥沙利铂联合氟脲嘧啶、亚叶酸钙治疗晚期胃癌临床观察

目的：观察奥沙利铂联合氟脲嘧啶、亚叶酸钙治疗晚期胃癌的疗效和安全性。方法：26例晚期胃癌，采用L-OHP130mg／m^2静滴4小时第1天；CF200mg／m^2静滴2小时后5-Fu500mg／m^2静滴4小时第1—5天，每三周重复。结果：26例晚期胃癌中，CR 2例(7．7％)，PR 11例(42．3％)，CR PR 50．0％。中位缓解期为5．5个月，中位生存期为11．0个月。毒性反应主要是感觉神经毒性(65．4％)，其次为恶心呕吐(53．8％)和腹泻(46．2％)。骨髓抑制毒性小。结论：L-OHP联合5-Fu、CF治疗晚期胃癌疗效肯定，耐受性良好，值得临床进一步应用。     

Oral doxifluridine in elderly patients with metastatic colorectal cancer: A multicenter phase II study

BACKGROUND: Cancer chemotherapy in elderly patients is an important andunder-researched area. Doxifluridine is a fluoropyrimidine derivativeand is activated to 5-fluorouracil by uridine phosphorylase,which is more highly expressed in malignant cells. Because ofthe high bioavailability and low toxicity of oral doxifluridinewe conducted this phase II trial to evaluate the feasibility,toxicity and activity of a home therapy with oral doxifluridinein elderly metastatic colorectal cancer patients. PATIENTS AND METHODS: Forty-three elderly metastatic colorectal cancer patients enteredthe study: their median ECOG performance status was 1 (0–2)and median age 74 years (69–83), the predominant siteof metastasis was liver and all but one of the patients hadreceived no previous chemotherapy. Doxifluridine was given orallyat the initial daily total dose of 2250 mg for 4 consecutivedays every week. The daily dose was reduced to 1500 mg if toxicitiesgreater than grade 2 (WHO) occurred. RESULTS: Forty-two patients are evaluable for toxicity: treatment waswell tolerated, with the most common side effect being diarrhea,severe in 7 (17%) patients (6 grade 3 and 1 grade 4). Thirty-sixpatients are evaluable for response and 2 complete and 3 partialresponses have been observed (response rate 14%; 95% confidencelimit interval 5%–29%). CONCLUSIONS: This study demonstrates that a home therapy with oral doxifluridinein elderly advanced colorectal cancer patients is feasible,with a relatively low rate of toxicity, and has moderate activity,comparable to that of intravenous 5-fluorouracil. Therefore,this treatment may be considered for the management of advancedcolorectal cancer in the elderly. doxifluridine, colorectal, elderly, advanced colorectal cancer     

Clinical administration of oxaliplatin for patients previously treated for refractory advanced or recurrent colorectal cancer

Oxaliplatin (L-OHP) was administered to 10 patients previously treated for refractory advanced or recurrent colorectal cancer. The number of times each had received previous chemotherapy treatment ranged from 1 to 5 (median 3) for durations of 2.5 to 52.8 (median 11.7) months. At the time, L-OHP was not yet approved for sale in Japan, and could only be imported from overseas for personal use. As this made it very expensive,we used a low L-OHP dose of 100 mg/body. Combinations with 5-FU were administered differently from previous regimens; these included chronotherapy, weekly high-dose, FOLFOX 4, and FOLFOX 6. L-OHP was administered from 1 to 14 times (median 4.5), and the response to treatment was PR in 2 patients and NC in 5.The response rate was 22.2%.Although in NC there was a tendency toward tumor reduction in 2 of the 5 patients, the treatment had to be suspended because of their financial situations. Overall survival from commencement of the first treatment was 3.1 to 58.7 months (median 17.6+) and after starting L-OHP was 0.6 to 17.2 months (median 6.4+). Adverse events included bone marrow suppression in three patients, 3 cases of leukocytopenia (grade 3 in two patients and grade 4 in one), grade 4 thrombocytopenia in one patient,grade 3 sensory disturbance in one patient,and grade 3 anorexia in two patients. All reactions were able to be controlled except for one patient with Grade 4 thrombocytopenia. In summary,treatment with L-OHP as salvage chemotherapy can possibly contribute to prolongation of survival time in cases of refractory advanced colorectal cancer.It is useful to combine L-OHP with high-dose continuous administration of 5-FU,namely FOLFOX regimens.FOLFOX 6 is the most useful of the FOLFOX regimens because it is simple and can be administered on an outpatient basis.     

A phase II study to determine the ability of gefitinib to reverse fluoropyrimidine resistance in metastatic colorectal cancer (the INFORM study)

There are data suggesting that inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase signalling may reverse resistance to fluoropyrimidine treatment. To investigate this further, the INFORM study was an open-label, non-comparative phase II study of gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE, USA) 250 mg daily in combination with 5-fluorouracil (5-FU administered as an intravenous 400 mg m(-2) bolus injection followed by 2800 mg m(-2) infusion over 46 h and folinic acid administered as a 350 mg infusion over 2 h) every 2 weeks for up to 12 cycles in 24 patients with metastatic colorectal cancer refractory to previous fluoropyrimidine treatment. There were no objective responses. The stable disease rate was 37.5% (95% CI: 18.80, 59.41), median progression-free survival measured 116 days and overall survival was 226 days. Quality of life was unchanged compared to baseline values, and the commonest toxicities were diarrhoea, rash and fatigue with 7 out of 24 (29%) patients having a grade 3 or 4 toxicity. Gefitinib does not sensitise patients with fluoropyrimidine refractory metastatic colorectal cancer to 5-FU chemotherapy.     

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer

BACKGROUND: The safety and efficacy of the fully human antibody panitumumab was evaluated in patients with metastatic colorectal cancer refractory to available therapies. METHODS: This phase 2 open-label, multicenter study of panitumumab enrolled patients with metastatic colorectal cancer who had progressed on chemotherapy that included a fluoropyrimidine and irinotecan or oxaliplatin, or both. All patients had tumors with > or =10% 1+ epidermal growth factor receptor (EGFr) staining by immunohistochemistry. Patients were stratified into 2 strata (high or low staining intensity) and received intravenous panitumumab 2.5 mg/kg weekly 8 of every 9 weeks until disease progression or unacceptable toxicity. RESULTS: In all, 148 patients received panitumumab, 105 in the high EGFr stratum, 43 in the low EGFr stratum. Overall response by central review was 9% (95% confidence interval [CI], 5%-15%) and was similar between strata. An additional 29% of patients had stable disease. Median progression-free survival was 14 weeks (95% CI, 8-16) and median overall survival was 9 months (95% CI, 6-10). Toxicities were manageable, with skin toxicity reported in 95% of patients (5% grade 3 or 4). Four patients discontinued therapy because of toxicity. No antipanitumumab antibodies were detected. One patient had an infusion reaction but was able to continue therapy. CONCLUSIONS: Panitumumab given weekly was well tolerated and had single-agent activity in previously treated patients with colorectal cancer. Dermatologic toxicity was common but rarely severe. Ongoing studies will determine panitumumab activity earlier in the course of treatment for colorectal cancer and in combination with other antineoplastic agents.     

艾素联合奥沙利铂治疗晚期结直肠癌的临床研究

为了观察艾素（多西他赛,DOC）联合奥沙利铂（L-OHP）治疗晚期结直肠癌的疗效和毒副反应,对34例晚期结直肠癌患者采用DOC联合L-OHP方案化疗,DOC75mg/m^2,静脉滴入,d1;L-OHP130mg/m^2,静脉滴入,d2;28d为1个周期,至少2个周期后评定疗效。结果示34例可评价疗效,其中完全缓解（CR）1例,部分缓解（PR）12例,总有效率（CR＋PR）为38.2%。中位生存期12个月。毒副反应主要为骨髓抑制、周围神经炎和脱发。初步研究结果提示,DOC联合L-OHP方案治疗晚期结直肠癌,缓解率高,毒副反应可以耐受。     

奥沙利铂联合5-FU/CF方案治疗晚期结肠癌的临床观察

目的:评价奥沙利铂(L-OHP)联合5-FU/CF方案治疗晚期结肠癌的临床疗效和不良反应.方法:43例晚期结肠癌患者,给予L-OHP 130mg/m2静脉滴注,持续4h,d1;CF 150mg/m2静脉滴注,持续2h,d1-d5;5-FU 500mg/m2静脉滴注,持续6h,d1-d5.每3周重复1次.结果:43例患者中,完全缓解(CR) 1例,部分缓解( PR) 11例,稳定( SD) 17例,进展( PD)11例,总有效率(CR + PR)34.9%.不良反应主要是末梢神经毒性、恶心呕吐、腹泻、骨髓抑制等,均可耐受.结论:L-OHP联合5-FU/CF方案治疗晚期结肠癌疗效好,不良反应主要是末梢神经毒性和胃肠道反应.