Activity of weekly irinotecan (CPT-11) in patients with advanced non-small cell lung cancer pretreated with platinum and taxanes

Irinotecan (CPT-11), a semisynthetic derivative of camptothecin, is active in the treatment of non-small cell lung cancer (NSCLC). In this report we describe our experience with this drug when used as a single agent in patients with advanced NSCLC refractory to chemotherapy with platinum and taxanes. Nineteen NSCLC patients (thirteen males and six females; 53% adenocarcinoma and 26% squamous cell carcinoma) with a median age of 52 years (range 34–71) and a Karnofsky performance status of 60% (60–80%) were included in the study. At baseline, the patients had a median of two disease sites and had been treated with a median of two prior regimens. Irinotecan was given at a dose of 100mg/m² i.v.) weekly for 4 weeks followed by 1 week of rest. A total of 123 weekly infusions were administered, and each patient received a median of 4 weeks of treatment (range 1–32). All patients were evaluated by intention-to-treat analysis for efficacy and safety. Main toxicities reported were grade 3 neutropenia (10% of patients), diarrhea (10% of patients), and grade 4 thrombocytopenia (5% of patients). The overall clinical response rate was 16% (95% CI: 8–24) with three partial responses and 9 (47%) patients with stable disease. The median time to progression and the median survival time were 7 and 15 weeks, respectively. In conclusion, weekly irinotecan showed antitumoral activity and minimum toxicity in NSCLC patients refractory to platinum and taxanes.     

A phase II study of rebeccamycin analog (NSC-655649) in metastatic renal cell cancer

Objective: Rebeccamycin analog (NSC-655649) is an antibiotic with antitumor properties demonstrated in preclinical and phase I studies. We conducted a phase II trial to evaluate the efficacy and toxicity of this agent in patients with advanced renal cell cancer (RCC). Methods: Eligible patients had histologically or cytologically confirmed diagnosis of RCC that was either locally advanced unresectable, locally recurrent, or metastatic. Patients had to have measurable disease, no prior chemotherapy, life expectancy of greater than 12 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, adequate-organ function, and be 18 years old. Patients were treated with NSC-655649 at a dose of 165mg/m² daily i.v. over 30–60min for 5 days. Treatment was repeated every 21 days. Response was assessed every two courses. Results: Twenty-four patients were enrolled. There were sixteen males and eight females with a median age of 60.5 years (range 42–76). Nineteen were Caucasians, seventeen had prior nephrectomy, and thirteen had prior immunotherapy. The major toxicity was myelosuppression with grade 3 and 4 neutropenia in 38% of patients and anemia in 33% of patients. There were two partial responses (2/24, 8%) and 11 patients (46%) achieved stable disease (SD). The 6-month progression-free rate for patients with SD was 30%. Of the seventeen patients with progressive disease at registration, one had a PR and eight had SD. The overall median survival time for all 24 patients was 10.0 months (90% CI=5.2, 17.4 months). The 12-month survival rate was 39%, with 90% CI=(0.21, 0.58). Nine patients are still alive with survival times ranging from 3.8 to 24.2 months, at a median follow-up time of 11.9 months. Conclusion: Rebeccamycin analog (NSC-655649) is well tolerated and has modest antitumor activity in patients with advanced RCC.     

Phase II evaluation of mitoxantrone in advanced pancreatic carcinoma: A Southwest Oncology Group study

Summary Patient with advanced adenocarcinoma of the pancreas and no prior chemotherapy were treated on a Phase II trial of mitoxantrone. Doses were adjusted for hepatic dysfunction as defined by bilirubin. Twenty-four patients with a bilirubin 1.5 mg% received mitoxantrone 12 mg/m² i.v. repeated every three weeks. Myelosuppression in the form of leukopenia was the major toxicity. There were no responses in twenty-four evaluable patients.     

紫杉醇联合洛铂腹腔化疗治疗晚期卵巢癌恶性腹水疗效观察简

目的观察紫杉醇联合洛铂腹腔灌注化疗治疗晚期卵巢癌恶性腹水的疗效和不良反应。方法收集2010年3月-2012年12月32例晚期卵巢癌患者合并恶性腹水,给予紫杉醇联合洛铂腹腔化疗,紫杉醇135mg／m^2静滴,第1天;洛铂30mg／m^2腹腔灌注,第2天;每4周1疗程。完成2个疗程后评价疗效并观察不良反应。结果全组32例均可评价疗效和不良反应,完全缓解（CR）10例,缓解率31．3％,部分缓解（PR）20例,缓解率为62．5％,总有效率为93．8％。主要不良反应为骨髓抑制,消化道反应轻,未见肝肾功能损害等毒副反应,无治疗相关性死亡。结论紫杉醇联合洛铂腹腔化疗治疗晚期卵巢癌恶性腹水不良反应轻,在短时间内显著控制腹水,改善患者生存质量,值得临床进一步观察和应用。     

Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma

We conducted a phase II evaluation of edatrexate in 17 previously untreated patients with advanced adenocarcinoma of the pancreas; 14 patients had at least one month of therapy. The initial dose was 80 mg/m²iv. Treatment was administered weekly for 5 weeks, then every other week. Toxicity was generally mild. The median WBC nadir was 5.4 (range 0.6–7.4)×10³/l, and the median platelet nadir was 164.0 (range 62.0–341.0)×10³/l. One patient died with sepsis and gastrointestinal bleeding associated with pancytopenia. Five patients had a mild rash. Nausea occurred in 6 patients, including 3 who had vomiting. In addition, 11 patients complained of vague malaise which seemed to begin within 24–48 hours after administration of edatrexate, and lasted for 2 to 3 days, resolving within 6 days of drug administration. Median survival was 85 days. Although 5 patients had stable disease, including one with relief of pain, no major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.     

Trimetrexate in advanced hormone-refractory prostate cancer

Summary The antitumor activity and toxicity of trimetrexate (TMTX) was evaluated in measurable, hormone-refractory, advanced prostate cancer patients. Patients were required to have an ECOG performance status < 3, bidimensionally measurable disease, serum creatinine 1.5 mg/dL, normal bone marrow function, and adequate hepatic function. Prior non-hormonal systemic therapy, active infection, third space effusions were exclusion criteria. TMTX 12 mg/m² daily for five days (8 mg/m² for patients with any prior radiation therapy or age 75 years) was administered every 3 weeks. There were no responses in the 18 eligible patients. Median time to treatment failure and median survival were 6 and 20 weeks, respectively. Myelosuppression was the most frequent toxicity observed and was mild to severe in all but 4 patients. Two patients whom experienced life-threatening reversible leukopenia and grade 4 thrombocytopenia developed in 2 further patients. Non-hematologic toxicity was also reversible and was mild to severe. TMTX at this dose and schedule is inactive in advanced, hormone-refractory prostate cancer.     

Phase II study of esorubicin (4 ′ deoxydoxorubicin) in anthracycline naive patients with ovarian cancer

Summary Sixteen patients with metastatic ovarian cancer who had not previously been treated with anthracyclines were treated with 4 deoxydoxorubicin at a dose of 30 mg/m² intravenously every 3 weeks. There were no clinical responses in this group of patients. Toxicities were infrequent with neutropenia and thrombocytopenia being dose limiting. Nausea and vomiting occurred in only 4 patients. We conclude that 4 deoxydoxorubicin is an inactive drug in this patient population and does not warrant further investigation in this disease.N. Colombo is a recipient of a fellowship from the American-Italian Foundation for Cancer Research.     

Phase II trial of trimetrexate in advanced esophageal cancer: A southwest oncology group study

Trimetrexate (TMQ) is a synthetic folate antagonist that has demonstrated non-cross resistance with methotrexate in preclinical screens. A phase II trial was performed with TMQ given to patients with advanced squamous cell carcinoma of the esophagus. TMQ was administered as an i.v. bolus on a daily × 5 schedule, every 3 weeks; a starting dose of 12 mg/m² was used for patients with no prior irradiation, and of 8 mg/m² for patients with prior irradiation. Twenty-four patients were entered onto study, with 23 patients eligible, and a median of 2 courses of TMQ administered per patient. Twenty-three patients were evaluable for toxicity. Toxicities of SWOG grade 3 included granulocytopenia (9 patients), leukopenia (7 patients), thrombocytopenia (4 patients), anemia (3 patients), mucositis (3 patients), nausea and vomiting (2 patients), dermatitis (1 patient), diarrhea (1 patient), and fever (1 patient). Fifteen patients had some hematologic toxicity, and eleven patients had hematologic toxicity of grade 3. Two treatment related deaths occurred in association with myelosuppression. One patient achieved a complete response and one patient achieved a partial response, with response durations of 8.5 months and 6 months, respectively. The overall response rate was 8% [95% confidence interval of 1 to 28%], with a median survival for the 23 eligible patients of 5.1 months.     

洛铂联合卡培他滨治疗蒽环类和紫杉类化疗失败的晚期乳腺癌的临床观察

目的探讨洛铂联合卡培他滨治疗蒽环类和紫杉类化疗失败的晚期乳腺癌的疗效及不良反应。方法36例蒽环类和紫杉类化疗失败的晚期乳腺癌患者,给予洛铂联合卡培他滨化疗：洛铂30mg／m^2,d1;卡培他滨每日2500mg／m。,分2次口服,d1～d14,3周为1周期。2周期后按wHO标准评价疗效及不良反应。结果36例患者均可评价疗效及不良反应,其中获CR2例,PR11例,SD12例,PD11例,有效率为36．1％,疾病控制率为69．49／6。主要不良反应为骨髓抑制和消化道反应,以1、2级为主,经对症处理后均可耐受。结论洛铂联合卡培他滨治疗蒽环类和紫杉类化疗失败的晚期乳腺癌的疗效较好,不良反应可耐受。     

Polyethylene glycol conjugated interleukin-2: Clinical and immunologic effects in patients with advanced renal cell carcinoma

Summary Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials employed different dose levels: A) 20x10⁶ I.U./m² day 1 followed by 12x10⁶ I.U./m² days 8, 15, 22; and B) 12x10⁶ I.U./m² days 1, 8, 15, 22. Thirty-five patients were entered and 31 were evaluable for response (A–15/18, B–16/17). Two of 31 patients had partial responses. Median therapy duration was four weeks (range 1–15), and dose reduction for grade III or IV toxicity was required in 14/35 patients (A-6/18, B-8/17). Toxicity ( grade III) seen included: hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No differences in response or toxicity between the two schedules were noted. Hematologic changes included lymphocytosis and eosinophilia in the majority of patients. PEG IL-2 given once weekly has significant toxicity, and may produce tumor regression in patients with renal cell carinoma.     

Phase II study of raltitrexed (Tomudex) in chemotherapy-pretreated patients with advanced colorectal cancer. Tomudex Cooperative Study Group

Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). This phase II study was conducted to evaluate the anti-timor efficacy and tolerability of raltitrexed in patients with advanced CRC who had received one previous chemotherapy regimen. Raltitrexed was administered at a dose of 3.0 mg/m2 i.v. over 15 min once every 3 weeks. Of 43 eligible patients, 53% had colon cancer and 47% rectal cancer. Objective responses were observed in 16% of patients [95% confidence interval (CI): 7-31%; seven partial responses). The median duration of response was 101 days (range: 45-239 days), the median overall duration of response was 145 days (range: 104-302 days) and the median survival was 11.6 months (95% CI: 9.4-14.7 months). Liver metastases showed a 17% (three of 18) response rate and lung metastases a 12% (three of 25) response rate. Adverse events of grade 3 or 4 reported for more than 5% of patients were neutropenia (23%), leukopenia (9%), reversible SGPT increase (7%) nausea/vomiting (19%), anorexia (14%), asthenia (9%) and hypotension (7%). Grade 3 or 4 diarrhea, stomatitis and alopecia were not observed. In summary, raltitrexed had an acceptable toxicity profile and promising anti-tumor activity against advanced CRC in patients who had received prior chemotherapy. Further clinical trials of combination chemotherapy using raltitrexed are warranted.     

Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients

Combination chemotherapy with docetaxel (T), cisplatin (P), fluorouracil (5-FU) and leucovorin has been reported to have major activity against squamous cell carcinoma of the head and neck (SCCHN) administered as a 4-day (TPFL4) or 5-day (TPFL5) regimen. The purpose of this study was to evaluate the efficacy and toxicity of a modified TPFL regimen (m-TPFL) for locally advanced SCCHN, consisting of a modified dosage with docetaxel, cisplatin, 5-FU and l-leucovorin (l-LV) designed for Japanese patients. Organ preservation of the primary tumor site was also assessed. Thirty-four Japanese patients with locally advanced SCCHN were eligible. Docetaxel was administered as a 1-h i.v. infusion at 48 mg/m2 on day 1; cisplatin, 24 mg/m2/day; 5-FU, 560 mg/m2/day and l-LV, 125 mg/body/day were delivered on days 1-4 by continuous i.v. infusion. This regimen was administered every 28 days. Patients who achieved a complete response (CR) after induction chemotherapy underwent radiation therapy alone. Ninety-one cycles were administered. The main hematological toxicity was neutropenia, classified as grade III or IV in 18.7% of cycles. The most common non-hematologic toxicities included anorexia, stomatitis and alopecia. The clinical overall response rate to m-TPFL was 88.2%, with 58.8% CRs and 29.4% partial responses. After definitive locoregional therapy, 25 of 34 patients were disease-free with preserved primary tumor site anatomy. Overall and progression-free survival rates at the 2-year follow-up are 92.8 and 75.3%, respectively. Our m-TPFL regimen designed for Japanese patients yielded excellent response rates with an acceptable toxicity profile in good-performance-status patients.     

Phase II trial of cisplatin and etoposide in patients with metastatic melanoma

Summary Fourteen patients with metastatic melanoma were treated with cisplatin and etoposide by bolus intravenous infusion daily for 5 consecutive days each month. All patients were evaluable for toxicity and twelve for response. Eight patients were treated with cisplatin 20 mg/m² and etoposide 100 mg/m² daily. Because of excessive myelosuppression, the daily dose of etoposide was reduced to 75 mg/m² in the remaining six patients. There were no major responses among 12 evaluable patients (major response rate 24% with 95% confidence). The median time to progression was one month. One patient with a liver metastasis had a minor response lasting 6 + months. The combination of cisplatin and etoposide in these doses and schedule lacked sufficient clinical efficacy in the treatment of metastatic melanoma.     

A phase II study of rebeccamycin analog NSC 655649 in patients with metastatic colorectal cancer

The analog, rebeccamycin tartrate salt (NSC 655649, Cancer Therapy Evaluation Program, National Cancer Institute) has broad preclinical anti-neoplastic activity. Preliminary data from phase I study demonstrated anti-tumor activity in colorectal carcinoma. This phase II trial evaluates its efficacy in patients with minimally treated metastatic colorectal cancer. Eligibility included Karnofsky performance status 70%, age 18 years and bidimensionally measurable disease. Thirteen patients were treated with NSC 655649 at 500mg/m² by central venous catheter once every 3 weeks by bolus injection. Thirty-four cycles (median [range] 2 [1–6]) of therapy were administered. Twelve patients are eligible for response assessment. No major objective responses were seen using the RECIST criteria; however stable disease was observed in three patients with mean duration of 15 weeks. The median time to progression was 8 weeks. There was no toxic death. Four patients received only one cycle of treatment, and three had disease progression. Toxicities were tolerable and hematologic toxicity was the most common. The median (range) granulocyte and platelet nadir counts were 2043/l (116–16,374/l) and 276×10³/l (5–769), respectively. Non-hematologic toxicities were moderate, including generalized weakness/fatigue, nausea/vomiting, diarrhea and anorexia. One patient required dose reduction; three patients required dose delays. NSC 655649 at this dose and schedule is inactive against advanced previously minimally treated metastatic colorectal cancer and further study of this drug as a single agent in this disease using an every three-week schedule is not warranted.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

Phase I/II study of cisplatin, 5-fluorouracil and α-interferon for recurrent carcinoma of the head and neck

Summary Current chemotherapy regimens have failed to demonstrate a significant impact on the overall survival of patients with recurrent head and neck cancer; therefore, new agents or combinations of agents are necessary to improve outcome. Alpha-interferon potentiates the activity in vitro of both agents of one of the most active regimens currently available, cisplatin and 5-fluorouracil. The purpose of the current study was to evaluate the feasibility and efficacy in patients with recurrent head and neck cancer of adding -interferon to cisplatin 14 mg/m² daily and 5-fluorouracil 700 mg/m² daily for 5 days. No significant toxicity occurred with -interferon at dose level 0,1 × 10⁶ units/m² daily for five days. Of four patients treated at dose level +1, -interferon 3 × 10⁶ units/m², two developed prolonged grade III neutropenic following the fourth course. One of three patients developed grade IV thrombocytopenia and 6 of 13 courses at this dose level resulted in grade III neutropenia. A phase II study was performed in 19 patients with cisplatin 17 mg/m²/ day, 5-fluoruracil 700 mg/m²/day and a-interferon 3 × 10⁶ units/m²/day. During the phase II study grade III neutropenia occurred in 6 patients and grade IV neutropenia in another patient during at least one course. Grade III and IV thrombocytopenia occurred in one patient each during the phase II study. Overall, major responses occurred in 7 or 23 patients (30%): 5 in phase I and 2 in phase II.In conclusion, the addition of -interferon to cisplatin and 5-fluorouracil is feasible, but does not appear to increase response rates in recurrent head and neck cancer.     

Phase I study of escalating dose mitoxantrone in combination with α-2-interferon in patients with advanced solid tumors

In vitro and preclinical in vivo data have shown a synergistic antitumor activity between -interferon and some antiproliferative agents. A phase I study of the concurrent administration of interferon- 2 and mito-xantrone was initiated, to determine the maximum tolerated dose of mitoxantrone given i.v. every 3 weeks in escalating doses combined with a fixed dose of s.c. interferon 2 (6 × 10⁶ IU three times per week³), in patients with advanced solid tumors resistant to conventional chemotherapy. At least three evaluable patients were entered in each dose level of mitoxantrone starting at 4 mg/m², with no escalations allowed in the same patient. Twenty-seven patients received a total of 101 cycles and five dose-levels were explored (4-6-8-10-12 mg/m² of mitoxantrone). The dose-limiting toxicities were leukopenia and granulocytopenia at 12 mg/m² of mitoxantrone, at which dose hematological toxicity occurred in > 50% of cases, with one patient presenting grade 4 leuko-granulocytopenia. No severe thrombocytopenia occurred. In the majority of patients transient hepatic enzyme elevations and a flu-like syndrome due to interferon a 2 were observed in all dose-levels explored. These observations suggest that the hepatotoxic effects of interferon a 2 do not emphasize mitoxantrone side-effects if given simultaneously. When mitoxantrone is administered with 6 × 10⁶ IU of interferon 2, the recommended dose for future phase II studies is 10 mg/m²/weeks³ with escalation up to 12 mg/m² in selected patients if such a combination is well tolerated in terms of myelosuppression. Regarding therapeutic activity, four out of 25 (16%) cases evaluable for response achieved a partial response. In conclusion the concomitant administration of recombinant interferon 2 and mitoxantrone allows the possibility to give a therapeutic dosage of both agents. Because the combination of the two agents was fairly well tolerated and antitumor activity was observed, phase II trials are warranted.     

Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hour continuous infusion weekly for three weeks in metastatic colorectal carcinoma

9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 g/m²/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/l (range 0–9,000/l) and occurred on day 10. Eight patients received an escalated dose of 600 g/m²/day. The median AGC nadir at the escalated dose was 1,500/l (range: 300–2,700/l) and occurred on day 22. The median number of courses given was 2 (range: 1–8); and the median time to disease progression was 8 weeks (range: 1–40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.     

A phase I and pharmacokinetic study of VNP40101M,a new alkylating agent,in patients with advanced or metastatic cancer

Summary Purpose: VNP40101M is a new alkylating agent that demonstrated broad anti-tumor activity in murine tumor models. A phase I trial was initiated to determine the toxicities, maximum tolerated dose, and pharmacokinetics of VNP40101M by short IV infusion. Study design: The starting dose was 3 mg/m² every four weeks, and was escalated in successive cohorts as follows: 6, 12, 24, 40, 60, 80, and 100 mg/m². Beyond 100 mg/m², dose increments were 25%. Initially, 1–2 patients were assigned to a dose level. Intra-patient dose escalation was permitted. With the first instance of a drug-related grade 2 adverse event, all dose levels required assessment of 3–6 patients. Pharmacokinetic parameters were assessed in the first cycle and any cycle with a change in dose. Results: Twenty-six patients in 13 dose levels ranging from 3–305 mg/m² were evaluated. Dose-related thrombocytopenia was the major toxicity, with the nadir occurring at a median of day 27. At 305 mg/m², six of eight patients developed grade 3 thrombocytopenia, including one event that met the definition for DLT. Other dose-related toxicities included moderate granulocytopenia, anemia, and a mild infusion-related syndrome consisting of acute headache and facial flushing. The granulocyte nadir occurred at a median of day 34, and recovery of both thrombocytopenia and neutropenia to < grade 2 occurred at a median of day 43. VNP40101M peak plasma concentrations and AUC were linear with dose. The elimination half-life was short and estimated to be approximately 15 minutes. Conclusions: The MTD and recommended dose for phase II trials is 305 mg/m² every six weeks. Phase II trials in less heavily pre-treated patient populations are warranted.Supported by Vion Pharmaceuticals, Inc.     

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 .