Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer

Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial. On the basis of sensitivity to previous treatment, 19 patients were considered as chemo-resistant and 14 patients as chemo-refractory. OXA 110 mg/m (over 2 h) and IRI 175 mg/m (over 1 h) were delivered on day 1, followed by LFA 250 mg/m (2-h infusion) plus 5FU 800 mg/m as intravenous bolus on day 2. Cycles were repeated every 2 weeks. A total of 348 cycles were delivered, with a median of nine cycles per patient (range, 1-12 cycles per patient). Five complete and 13 partial responses were reported on 40 assessable patients, giving a response rate of 45% [95% confidence interval (CI), 29-62%]; eight of 19 (42%) resistant patients and five of 14 (36%) refractory patients achieved a major response, which was also obtained in four of eight (50%) patients pretreated with IRI and in three of eight (38%) patients pretreated with OXA. Grade 3 or higher neutropenia occurred in 68% of patients, but febrile neutropenia or infections affected only seven (17%) patients. No episodes of grade 3 or higher thrombocytopenia or anemia were recorded. Occurrence of severe non-hematologic toxicities by patients were: diarrhea, 34%; vomiting, 17%; peripheral cumulative neuropathy, 15%; stomatitis, 10%; acute cholinergic syndrome, 7%. Actually delivered dose intensities of all three drugs resulted in about two-thirds of the planned ones. After a follow-up of 39 months, median progression-free survival was 7.5 months. Median overall survival was 14.4 (95% CI, 10.4-18.4) months from the start of OXIRIFAFU and 25.3 (95% CI, 18.1-32.5) months from the diagnosis of metastatic disease. This OXIRIFAFU triplet regimen was highly effective in resistant/refractory colorectal cancer patients. A slight dose reduction of all cytotoxic drugs could be advisable in order to improve the tolerability of this regimen without jeopardizing its activity.     

奥沙利铂联合亚叶酸钙和氟尿嘧啶治疗晚期大肠癌的临床观察

目的评价奥沙利铂联合亚叶酸钙和大剂量氟尿嘧啶（5-FU）持续48 h静脉滴注治疗晚期大肠癌的疗效和安全性。方法32例大肠癌患者采用静脉滴注奥沙利铂100 mg/m^2,亚叶酸钙200 mg/m^2,亚叶酸钙滴注之后用5-FU 0．5 g静注,接着用5-FU 3．0 g/m^2持续静脉滴注48h,每2周1次,2次为1个周期。结果32例病例中,平均疗程数为4个周期,其中完全缓解（CR）1例,部分缓解（PR）15例,稳定（SD）12例,进展（PD）4例,总有效率（CR＋PR）为50%。不良反应为恶心、呕吐和骨髓抑制,但多为Ⅰ～Ⅱ度,一过性感觉异常。结论奥沙利铂联合亚叶酸钙和氟尿嘧啶治疗晚期大肠癌疗效较高,不良反应轻而且安全,患者容易耐受,值得推广使用。     

Second-line treatment with oxaliplatin,leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study

Study objectives: The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas. Patients and methods: Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m² (2-hour iv infusion), followed by Leucovorin 50 mg/m² (i.v. bolus) and 500 mg/m² 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria. Results: A total of 30 patients, 20 men and 10 women, median age 63 years (range 52–71 years) and Karnofsky Performance Status (PS) of ≥50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths. Conclusions: The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients. An erratum to this article is available at .     

奥沙利铂联合5-氟尿嘧啶、亚叶酸钙治疗化疗失败的晚期胃癌的临床观察

目的 观察奥沙利铂联合5-氟尿嘧啶、亚叶酸钙治疗化疗失败的晚期胃癌患者的临床疗效及不良反应.方法 36例患者均经组织病理学证实及有可评价病灶.采用奥沙利铂130 mg/m2,亚叶酸钙(LV)200 mg/m2及5-氟脲嘧啶(5-Fu)500 mg/m2～5方案化疗.3周为1周期,2周期评价疗效.结果 36例患者均至少完成2周期化疗,均可评价疗效和不良反应.全组CR患者3例(8.3%),PR11例(30.6%),SD12例(33.3%),PD10例(27.8%).有效率为38.9%.主要不良反应为血液系统毒性、粘膜炎与感觉神经毒性.结论 奥沙利铂联合5-氟脲嘧啶、亚叶酸钙治疗化疗失败的晚期胃癌患者有一定的客观缓解率,不良反应可以耐受,值得进一步研究.     

奥沙利铂联合5-氟尿嘧啶和亚叶酸钙治疗晚期胃癌的临床研究

目的观察奥沙利铂联合5-氟尿嘧啶(5-FU)和亚叶酸钙(CF)治疗晚期胃癌临床疗效及其不良反应。方法奥沙利铂100 m g/m 2,静脉滴注2 h,第1天;CF 400 m g/m 2,静脉滴注,第1天;5-FU 400 m g/m 2,静脉推注,第1天;后续5-FU 2600 m g/m 2,静脉持续输注46 h;每2周重复,应用4次奥沙利铂(8周)后判断疗效。结果46例患者中,完全缓解(CR)5例(11%),部分缓解(PR)18例(39%),稳定(SD)16例(35%),进展(PD)7例(15%),CR+PR共23例,近期客观有效率为50%。26例初治患者中,CR 5例,PR10例,SD 8例,PD 3例,有效率58%;20例复治患者中,CR 0例,PR 8例,SD 8例,PD 4例,有效率40%,中位缓解时间为5个月,中位生存期为9个月。主要毒副反应为神经毒性,恶心、呕吐、白细胞和血小板减少程度较轻。结论奥沙利铂联合5-FU/CF治疗晚期胃癌有较好的近期疗效,毒副反应轻而且安全。     

An economic evaluation of Tomudex (raltitrexed) and 5-fluorouracil plus leucovorin in advanced colorectal cancer.

Our objective was to establish the balance between costs and effects of treatment with Tomudex (raltitrexed) as an alternative to treatment with 5-fluorouracil (5-FU) plus leucovorin (LV) in patients with advanced colorectal cancer. Data were used from an international, open label randomized clinical trial. Costs were calculated by multiplying resource utilization data with Dutch estimates of unit costs. Effects have been expressed in terms of 6 months and 1 year survival, and in terms of the number of patients without severe adverse events including WHO grade 3 and 4 leucopenia, mucositis, anemia and severe asthenia. Cost effectiveness is expressed in terms of costs per additional day of survival and costs per additional patient without any severe adverse event. The clinical results did not show significant survival differences implying great uncertainty about the cost-effectiveness of raltitrexed in terms of additional costs per additional life-year gained. However, 80% of the initially higher cost of raltitrexed ($3132 per patient) is compensated by savings due to a more convenient administration scheme leading to a net cost of $626 per patient treated. Weighed against the decrease in adverse events, a cost-effectiveness ratio results of $3936 per additional patient free of any severe adverse event. More favorable estimates result when the convenience of the administration scheme is valued in positive monetary terms.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗铂耐药复发卵巢癌初探

目的探讨奥沙利铂(L-OHP)联合氟尿嘧啶(5-FU)和亚叶酸钙(LV)治疗晚期复发性卵巢癌的临床效果。方法对6例铂耐药复发卵巢癌患者行L-OHP联合5-FU、LV方案化疗,每3周重复,观察其临床效果及毒副反应。结果疗效评定4例部分有效(PR),1例稳定(SD),1例进展(PD),毒副反应均不严重。结论奥沙利铂联合5-FU、LV治疗铂耐药复发卵巢癌有一定疗效,值得进一步研究。     

奥沙利铂联合亚叶酸钙及氟尿嘧啶治疗晚期大肠癌的临床分析

目的观察奥沙利铂联合亚叶酸钙及氟尿嘧啶方案治疗晚期大肠癌的临床疗效及毒副反应。方法 64例晚期大肠癌患者给予化疗方案为:L-OHP 130 mg/m2静脉点滴2 h,d1;CF 200 mg/m2,静脉点滴2 h,d1;5-FU 400 mg/m2静脉推注,后2 400 mg/m2微泵持续静脉滴注48 h。每2周重复,4周为1个周期,完成2个周期后判定疗效,按WHO标准评价客观疗效和毒副反应。结果全组64例均可评价疗效,其中完全缓解8例,部分缓解24例,稳定18例,进展14例,总有效率CR+PR=50.0%。中位肿瘤进展时间为5.6个月,中位生存时间为9.5个月。毒副反应主要是骨髓抑制、胃肠道反应及外周神经毒性。结论奥沙利铂联合亚叶酸钙及氟尿嘧啶方案治疗晚期肠癌患者的近期疗效较好,毒副反应可以耐受,值得进一步研究应用。     

Phase I trial of sequential raltitrexed followed by bolus 5-fluorouracil in patients with advanced colorectal cancer

Our objective was to determine the maximum tolerated dose (MTD) of sequential raltitrexed (Tomudex) and 5-fluorouracil (5-FU) by bolus administration every 3 weeks in patients with advanced colorectal cancer (aCRC) and appendiceal adenocarcinoma. This phase I dose-escalation study was carried out in three stages: (1) 5-FU fixed at 900 mg/m, raltitrexed escalated from 0.5 to 3.0 mg/m, (2) raltitrexed fixed at 3.0 mg/m, 5-FU escalated from 900 mg/m until dose-limiting toxicity (DLT) and (3) 5-FU fixed at the dose level below DLT, raltitrexed escalated from 3.0 mg/m until MTD. Seventy-one patients with measurable disease were enrolled. No DLTs were observed during stage 1 of treatment. At a fixed dose of raltitrexed 3.0 mg/m, DLT developed when 5-FU was increased to 1350 mg/m (stage 2). When 5-FU was fixed at 1200 mg/m and raltitrexed was increased to 6.0 mg/m (stage 3), DLT was dose limiting. The recommended doses for further study are 5.5 mg/m ralitrexed and 1200 mg/m 5-FU. Of the 69 patients evaluated for efficacy, one had a complete response (8.0 months) and five had partial responses (5.1-11.6 months). Thirty patients had stable disease for 5 or more cycles of therapy (mean time to progression: 3.6 months). Median survival was 11.7 months. We conclude that raltitrexed can be combined with bolus 5-FU, at raltitrexed doses that are higher than the recommended single-agent dose of 3.0 mg/m, with manageable toxicity. This combination shows encouraging activity, and survival appears promising in the pre-treated aCRC patient population. Further clinical trials are warranted.     

Irinotecan (CPT-11) combined with bolus 5-fluorouracil/leucovorin (Saltz regimen) as first-line chemotherapy of patients with advanced colorectal cancer

Concerns about the safety of irinotecan (CPT-11) plus bolus 5-fluorouracil (5-FU)/leucovorin (LV) (the so-called Saltz regimen) have been previously reported. This prospective, multicenter, non-randomized study evaluated the anti-tumoral effect and toxicity of the Saltz regimen as first-line chemotherapy of 130 patients with advanced colorectal cancer (CRC). The median numbers of treatment cycles and infusions received per patient were 3 and 12, respectively. Eight (6.1) and 37 patients (28.5%) showed complete and partial responses, respectively [overall response rate=34.6% (95% confidence interval=20.7-48.5%)]. After a median follow up period of 9 months, 70 patients had died. The median progression-free survival and overall survival were 6.78 (0.3-33.8) and 8.26 months (range 0.3-33.8), respectively. The combined CPT-11/5-FU/LV treatment was well tolerated and no toxic deaths were reported. The most common grade 3/4 hematological toxicity was neutropenia (28% of patients and 3% of infusions), but no febrile neutropenia was reported. Delayed diarrhea was the most reported grade 3/4 non-hematological toxicity (21% of patients and 2% of infusions). Other non-hematological toxicities showed very low incidences. During the study five patients died due to factors not associated with disease progression. We conclude that the Saltz regimen administered on an outpatient basis was safe and well tolerated in patients with advanced CRC. Close monitoring of external patients together with an early treatment of toxicity was found to be essential to prevent severe and potentially fatal gastrointestinal or thromboembolic events previously reported with this CPT-11 combined regimen.     

Phase II study of oxaliplatin in combination with continuous infusion of 5-fluorouracil/leucovorin as first-line chemotherapy in patients with advanced gastric cancer

This study was designed to determine the efficacy and safety of biweekly oxaliplatin in combination with infusional 5-fluouracil (5-FU) and leucovorin in patients with advanced gastric cancer (AGC). Fifty-five eligible patients with measurable or assessable M/AGC (median age 62 and 90% of patients presented with metastasis) received oxaliplatin (85 mg/m2) intravenous infusion for 2 h, followed by intravenous infusion of 5-FU (3000 mg/m2) and leucovorin (100 mg/m2) for 46 h every 14 days until the patient's disease was either in progression, unacceptable toxicity, patient's withdrawal or the investigators' decision to discontinue treatment. Of the 55 enrolled patients, 48 were evaluable for response. Three patients (5.4%) showed complete remission and 20 patients (36.4%) achieved partial response. The overall response rate was 47.9%. Nineteen patients (34.5%) had stable disease and six patients (10.9%) showed progressive disease. The median time to progression was 5.6 months and the median overall survival was 10.8 months. Grade 3/4 toxicities included leucopenia (12.7%), thrombocytopenia (5.4%), diarrhoea (3.6%) and vomiting (9.1%). Peripheral neuropathy was noted in 61.8% of the patients (grade 1/2: 54.5%; grade 3: 7.3%). Our study confirmed that the combination of oxaliplatin and continuous infusion of 5-FU/leucoverin without bolus 5-FU as first-line chemotherapy is active for patients with AGC and relatively safe with lower haematological toxicity.     

奥沙利铂分别联合卡培他滨和替吉奥治疗晚期结直肠癌的临床疗效分析

目的 探讨奥沙利铂分别联合卡培他滨和替吉奥两种治疗方案对晚期结直肠癌的临床疗效及不良反应比较,为临床应用提供理论和实践的依据。方法 选取68例符合入组标准的晚期结直肠癌患者,按照用药方案的不同分成卡培他滨联合奥沙利铂治疗组(A组)35例,替吉奥联合奥沙利铂组(B组) 33例,通过观察两组方案的近期疗效、疾病进展时间及不良反应,分析评价两种方案的临床效果。结果 两种方案的近期疗效、疾病进展时间和不良反应发生情况,差异无统计学意义(P>0.05)。结论 卡培他滨联合奥沙利铂与替吉奥联合奥沙利铂治疗晚期结直肠癌疗效相当,不良反应差异无统计学意义,两种方案均可作为晚期结直肠癌患者治疗的较好选择。     

Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer

The primary aim of this study was to evaluate the toxicity (mucositis, diarrhea and leucopenia) of a therapy with 5-fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, Laves coli extract, Colibiogen inject, cell-free soluble fraction from lysed E. coli, Laves strain) in comparison with 5-FU plus placebo. Secondary endpoints included general toxicity, response rate according to WHO, survival time and quality of life. 164 patients with advanced colorectal cancer were enrolled in this randomised, placebo-controlled, double-blind, multicenter phase III study. The treatment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m2/d 5-FU on five consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 verum, 72 placebo) evaluable for response. The therapy with LC-Extract was well tolerated. Adverse events that occurred during the study were mainly judged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m2/d 5-FU in both treatment groups was very low. After treatment with 750 mg/m2/d 5-FU patients in the placebo-group experienced a higher CTC toxicity than in the LC-Extract groups. Remission rate and survival time showed a slight trend in favour of LC-Extract. These results suggest a positive benefit-risk ratio of the additional application of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU.     

A Phase II trial of weekly infusional 5-fluorouracil in combination with lowdose leucovorin in patients with advanced colorectal cancer

Exogenous leucovorin is a source of reduced folate which enhances the inhibition of thymidylate synthase that results from 5-fluorouracil (5-FU) administration. Extracellular reduced folate concentrations of 1 M have been reported to yield maximal enzyme inhibition in several cell lines treated with 5-FUin vitro. Clinical studies indicate that low doses of leucovorin have equivalent efficacy to higher doses in successfully modulating 5-FU in the treatment of colorectal cancer. Based on pharmacokinetics at higher doses, steadystate total plasma reduced folate concentrations of 1 M would be expected from the administration of leucovorin 50 mg/m² by 24 h infusion. This dose was admixed with 5-FU 2300 mg/m² and administered by 24 h infusion weekly to 38 patients with advanced colorectal cancer, of whom 32 are evaluable for response. Disease sites included liver (33 patients), lung (12 patients), and bone (4 patients). Toxicity was mild to moderate, except for grade 3 diarrhea in 5 patients, and chest pain in 2 patients. Among the 32 evaluable patients, there were 14 partial remissions for a total response rate of 44% (95% confidence interval 27–61%). The median duration of response was seven (range 1 to 20+) months, and median duration of survival 16 months. These results support the use of low doses of leucovorin to modulate weekly infusional 5-FU in colorectal cancer, and provide a basis for the integration of this regimen with other modulators of 5-FU.     

顺铂联合5-氟尿嘧啶与奥沙利铂联合替吉奥一线治疗晚期胃癌的对比研究

目的比较顺铂(DDP)联合5-氟尿嘧啶(5-FU)与奥沙利铂(L-OHP)联合替吉奥(S-1)一线治疗晚期胃癌的有效性和安全性。方法回顾性分析该院2009年1月-2012年11月间收治的53例晚期胃癌患者,其中A组(DDP+5-FU,PF组)25例,具体为:DDP 20 mg·m-2静滴,第1～5天,5-FU 500 mg·m-2静滴维持24 h第1～5天,每4周重复。B组(L-OHP+S-1)28例,具体为:L-OHP 130 mg·m-2静滴2 h,第1天,S-1 40 mg·m-2早晚2次餐后服用,第1～14天,每3周重复。每2个周期评价疗效及毒性。结果 53例患者均可评价毒副反应和近期疗效,44例可评价远期疗效。A组中有效率和疾病控制率分别为44%和56%,B组中有效率和疾病控制率分别为53.6%和89.3%,两组差异均无统计学意义(P0.05)。A组中位疾病进展时间(TTP)和中位总生存时间(MST)分别为4.5个月和10.7个月,B组中位TTP和中位MST分别为8.0个月和13.0个月。两组中位TTP差异有统计学意义(P=0.032),中位MST差异无统计学意义(P=0.172)。两组毒副反应主要有血液学异常、肝肾功能异常、恶心呕吐、神经毒性等,以1～2级为主,可耐受,B组轻度神经毒性发生率明显高于A组,差异有统计学意义(P=0.012)。结论 S-1+L-OHP方案一线治疗晚期胃癌,同PF方案相比中位疾病进展时间延长,毒副反应均可耐受,给药方便,值得临床进一步研究。     

FOLFOX方案治疗30例晚期胃癌疗效观察

目的：观察每二周高剂量亚叶酸钙（CF）／氟脲嘧啶（5－FU）与草酸铂（L－OHP）方案（FOLFOX方案）治疗晚期胃癌的临床疗效和毒副反应。方法：采用高剂量CF／5－FU／L－OHP深静脉输注方案（CF200mg.m^2-1.d^-1，静滴2小时，第1、2天；5-FU400mg.m^2-1.d^-1,静推，第1天，5－FU1600mg.m^2-1.d^-1，静滴22小时，第1、2天；L－OHP130mg.m^2-1.d^-1，静脉输注4小时，第1天），化疗方案以14天为1周期，重复4周期后间隔1个月评定疗效。结果：全组30例，总有效率为53．3％，18例初治组的有效率为61．11％，其中CR1例。12例复治组的有效率为41．7％，初治组中位缓解期为5个月。复治组的中位缓解期为3个月。Ⅱ、Ⅲ度口腔炎发生率为26．7％，7例出现手足综合征，血液学毒性轻微。结论：每二周高剂量CF／5－FU／L－OHP方案是治疗晚期胃癌有效安全的化疗方案。     

Phase II study of epirubicin plus oxaliplatin and infusional 5-fluorouracil as first-line combination therapy in patients with metastatic or advanced gastric cancer

The purpose of this study was to evaluate the efficacy and safety of an epirubicin, oxaliplatin and infusional 5-fluorouracil combination in patients with advanced gastric cancer. Patients with previously untreated advanced measurable gastric cancer received epirubicin (50 mg/m2, day 1), oxaliplatin (130 mg/m2 2-h infusion, day 1) and 5-fluorouracil (750 mg/m2, 24-h infusion, day 1-3) every 3 weeks. The primary endpoint of this phase II study was the response rate according to Response Evaluation Criteria in Solid Tumors. Out of 48 patients, 46 were evaluable for efficacy and 48 for toxicity. A median of five cycles (range 1-6) was administered. The overall best response rate was 47.8% (95% confidence interval 33-63%) including 2.2% complete responses and 45.6% partial responses. The median time for progression and median overall survival was 5 (95% confidence interval 4.1-5.9) and 11 months (95% confidence interval 8.1-13.9), respectively. Grade 3/4 neutropenia and leukocytopenia were observed in 25 and 12.5% of patients, respectively. Grade 3/4 nonhematological toxicities included nausea (6.3%), vomiting (14.6%), neurological toxicity (10.4%) and mucositis (2.1%). The epirubicin, oxaliplatin and infusional 5-fluorouracil regimen was effective and well tolerated as a front-line chemotherapy for patients with metastatic or advanced gastric cancer, and should be evaluated further.     

Phase I study of gefitinib, oxaliplatin, 5-fluorouracil, and leucovorin (IFOX) in patients with advanced solid malignancies

Summary Purpose: Aphase 1 study of gefitinib in combination with oxaliplatin, 5-fluorouracil and leucovorin (IFOX)was conducted to evaluate the safety and feasibility of this regimen. Patients and Methods: Patients with advanced solid malignancies were treated with escalating doses of gefitinib (250 mg or 500 mg once daily) in combination with FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin). The initial dose of oxaliplatin was 70 mg/m2 with sequential dose escalation to 85 mg/m2. Results: Sixteen patients received a total of 138 14-day courses of daily gefitinib in combination with FOLFOX. Escalation of gefitinib from 250 mg/d to 500 mg/d with FOLFOX was well-tolerated. In addition, no severe toxicities precluded subsequent dose escalation of oxaliplatin from 70 mg/m2 to 85 mg/m2 at which no dose-limiting toxicity was seen. No further dose escalation was performed as this represented the oxaliplatin dose administered in the standard FOLFOX-4 regimen. The most predominant toxicity was diarrhea, which was well controlled with oral antidiarrheal agents. Four partial remissions occurred in patients with metastatic colorectal cancer. Conclusions: Gefitinib as a 500 mg daily continuous dose was well tolerated in combination with full doses of FOLFOX-4.