Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group

Purpose  This phase II trial assessed the tolerability and efficacy of a triplet of oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer. Methods  Patients with unresectable or metastatic gastric cancer, unexposed to palliative chemotherapy, received oxaliplatin 85 mg/m² iv and irinotecan 150 mg/m² iv on day 1, 6S-folinic acid 250 mg/m² iv and fluorouracil 750 mg/m² iv on day 2, every 2 weeks. Response rate (RR) was assessed after a minimum of four cycles, and treatment continued up to 12 cycles. Results  Sixty-three patients were treated, with a median of eight (range 1–12) cycles/patient. Two complete and 19 partial responses were registered (RR 33% [95% CI, 22–46%]). Median progression-free survival was 7.5 (95% CI, 5.6–9.4) months, and median overall survival was 12.1 (95% CI, 10.8–13.4) months. Most common grade ≥3 toxicities were neutropenia (59%), febrile neutropenia (7%), vomiting (20%), and diarrhoea (10%). All-grade neurotoxicity affected 33% of patients. Conclusions  Oxaliplatin, irinotecan, and fluorouracil/folinic acid administered every 2 weeks are safe and active in advanced gastric cancer. SICOG trial 0405, EudraCT number 2006-0066869-16.     

Brain metastases from colorectal carcinoma: prognostic factors and outcome

Brain metastases from colorectal carcinoma (CRC) are rare. The objectives of this study are to assess the natural history, outcome, and possible prognostic factors in CRC patients with brain metastases. Between 1995 and 2008, 8,732 patients with CRC were treated at Yonsei University Health System. Brain metastases were found in 1.4% of these patients. Retrospective review and statistical analysis of these 126 patients were performed. Median time from diagnosis of metastatic CRC (mCRC) to brain metastases was 9.0 months (range 0–85 months), and 14 patients (11.1%) had brain involvement as their initial presentation. Among the 126 patients, 91.3% had other systemic metastases; the most common extracranial metastatic site was lung (72.2%). Median follow-up duration was 6.1 months (range 0.1–90.3 months), and median survival after diagnosis of brain metastases was 5.4 months [95% confidence interval (CI) 3.9–6.9 months]. Median survival time after diagnosis of brain metastases was 1.5 months for patients who received only steroids (15.9%), 4.0 months for those who received whole-brain radiation therapy (37.5%), 9.5 months for those who received gamma-knife surgery (GKS) (32.5%), and 11.5 months for those who underwent surgery (20%) (P < 0.001). On multivariate analysis, recursive partitioning analysis (RPA) class and amount of chemotherapy before brain metastasis were independent prognostic factors for survival. Overall prognosis of patients with brain metastases from CRC is poor. Nevertheless, patients with low RPA class, or those with previous less chemotherapy showed good prognosis, indicating that proper treatment may result in improved survival time.     

晚期结直肠癌内科治疗进展

晚期转移性结直肠癌的5年生存率低于10％。5-FU／LV方案治疗的中位生存期大约12个月。最近化疗方案的更新延长了患者的中位生存期。研究发现奥沙利铂、伊立替康联合5-FU／LV或者卡培他滨等化疗方案使中位生存期延长到20个月。奥沙利铂，伊立替康联合5-FU／LV比传统的单药5-FU／LV使生活质量改善时间延长。目前转移性结直肠癌标准的一线治疗方案为FOLFOX和FOLFIRI。正在进行的研究关注新的分子靶向药物（molecular targeted therapy）联合化疗治疗转移性结直肠癌，且部分试验取得了较好的疗效。本文将对5-FU、新一代化疗药物以及分子靶向药物在转移性结肠癌治疗的演进及新进展作一综述。     

Chronomodulated administration of oxaliplatin plus capecitabine (XELOX) as first line chemotherapy in advanced colorectal cancer patients: phase II study

Background The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. The aim of the present study was to define the feasibility and efficacy of XELOX administered through a new chronomodulated schedule in untreated advanced colorectal cancer (CRC) patients. Methods Chemotherapy-naive patients with advanced CRC were considered eligible for the study accrual. Treatment: oxaliplatin 70 mg/m² continuous infusion (c.i.) for 12 h (8:00 a.m. to 8:00 p.m.) days 1, 8 plus chronomodulated oral capecitabine 1,750 mg/m²/die (h 8:00 a.m. 25% of total dose; h 6:00 p.m. 25% of total dose; h 11:00 p.m. 50% of total dose), days 1–14 every 21 days. Results Forty-six patients were evaluated for safety and efficacy (male/female, 20/26). Median age was 64 years (range 28–77 years). Median Eastern Cooperative Oncology Group performance status (PS) was 0 (range 0–1). A total of 324 cycles have been administered: median per patient 6 (range 3–10 courses). Median number of metastatic sites was 1. Metastatic sites distribution was as follows: liver (65.2%), lung (34.8%), and nodes (32.6%). Median follow-up was 14 months (range 6.0–40.3 months). In an intent-to-treat efficacy analysis, objective response and stable disease were recorded in 27 (58.6%) and in 16 patients (34.9%), respectively. The median response duration was 8.0 months (95% CI; 5.03–10.96 months). The median time to progression (TTP) was 9.0 months (95% CI; 6.47–11.52 months). The overall survival (OS) was not reached, with a median value > 24 months (95% CI; 23.66–36.30 months). The grade 3 toxicities were diarrhea (8.7%), liver toxicity (13.1%), fatigue (8.7%), neurotoxicity (2.2%), neutropenia (8.7%), and thrombocytopenia (2.2%). Conclusion This regimen resulted of particular interest for patients with untreated metastatic CRC.     

The efficacy and safety of hepatic arterial infusion of oxaliplatin plus intravenous irinotecan,leucovorin and fluorouracil in colorectal cancer with inoperable hepatic metastasis

Hepatic arterial infusion (HAI) was evaluated for different drugs to treat hepatic metastasis from colorectal cancer (CRC). Combination treatment with 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) is effective for CRC. A phase II study was conducted to evaluate concomitant HAI administration of oxaliplatin and intravenous leucovorin, 5-FU and irinotecan (FOLFIRI) for patients with inoperable liver metastasis, which had chemotherapy with oxaliplatin (OX) 85?mg/m² HAI plus systemic intravenous chemotherapy [leucovorin 200?mg/m², 5-FU 2400?mg/m² and irinotecan (IRI) 160?mg/m² in 48 hours]. We treated 24 patients. Neutropaenia was the most frequent toxicity. The main HAI-related toxicity was pain. Two patients (8%) obtained complete response and 17 patients (70%) partial response, giving an objective response rate of 78%. Median follow-up was 22.8 months, and median overall and disease-free survival times were 29 and 20 months, respectively. Therefore, OX HAI and intravenous FOLFIRI is feasible and effective in patients with metastatic CRC.     

Advances in the treatment of metastatic colorectal cancer

The overall 5-year survival rate for patients with metastatic colorectal cancer (CRC) is less than 10%. Median survival with 5-fluorouracil (5-FU)/leucovorin (LV) therapy is approximately 12 months. Recent additions to the chemotherapy armamentarium for this disease have begun to prolong median survival times. In trials in which patients are exposed to all three approved chemotherapy agents, oxaliplatin, irinotecan, and 5-FU/LV, or capecitabine during the course of their disease, median survival has reached 20 months. The addition of oxaliplatin and irinotecan to 5-FU/LV regimens has also led to the maintenance of quality of life for longer intervals than were traditionally observed with 5-FU/LV alone. Current standard first-line regimens for metastatic CRC are FOLFOX (infusional 5-FU/LV with oxaliplatin) and FOLFIRI (infusional 5-FU/LV with irinotecan). The addition of bevacizumab to a two-drug regimen (irinotecan with 5-FU/LV) prolongs median survival to 20 months, with a modest amount of additional toxicity. Improvements in this median survival have not yet been realized with modifications to the current standard regimens; however, the oral agent capecitabine appears to be a reasonable substitute for infusional 5-FU/LV in combination regimens or as a single agent, with the advantage of reducing the inconvenience of the long infusion time. Ongoing investigations will identify a place for capecitabine, epidermal growth factor inhibitors, and new cytotoxics in the treatment of metastatic CRC.     

A phase II trial evaluating capecitabine and irinotecan as second line treatment in patients with oesophago-gastric cancer who have progressed on, or within 3 months of platinum-based chemotherapy

Rationale  There is no standard second line therapy for relapsed oesophago-gastric (O-G) cancer. Methods  We recruited 29 eligible patients with relapsed O-G cancer who had progressed during or within 3 months of prior chemotherapy to assess the efficacy and toxicity of capecitabine [2,000 mg/(m² day) on days 1–14] and irinotecan (250 mg/m²) given every 3 weeks. Results  Five patients (17%) demonstrated objective response, while a further seven patients (24%) achieved disease stabilisation. Median progression-free survival and overall survival were 3.1 months (95% CI = 2.2–4.1 months) and 6.5 months (95%CI = 6–7.1 months), respectively. Among symptomatic patients, palliation of tumour-related symptoms included resolution of reflux (5/12 pts), dysphagia (3/9 pts) and weight loss (4/9 pts), improvements in anorexia (4/10 pts), nausea (3/4 pts), vomiting (4/6 pts) and pain (4/16 pts). Grade 3–4 toxicities were diarrhoea (15%), nausea and vomiting (7%), lethargy (31%), neutropenia (31%), anemia (14%) and thrombocytopenia (7%). Conclusions  Capecitabine and irinotecan has anti-tumour activity as second line treatment for relapsed O-G cancer, and provides an important improvement in disease related symptoms.     

Shortened time interval between colorectal cancer diagnosis and risk testing for hereditary colorectal cancer is not related to higher psychological distress

Current diagnostic practices have shortened the interval between colorectal cancer (CRC) diagnosis and genetic analysis for Lynch syndrome by MSI-testing. We studied the relation of time between MSI-testing since CRC diagnosis (MSI–CRC interval) and psychological distress. We performed a cross-sectional study in 89 patients who had previously been treated for CRC. Data were collected during MSI-testing after genetic counseling. Psychological distress was measured with the IES, the SCL-90 and the POMS; social issues with the ISS, ISB and the ODHCF. The median time of MSI–CRC interval was 24 months (range 0–332), with 23% of the patients diagnosed less than 12 months and 42% more than 36 months prior to MSI-testing. In 34% of the patients cancer specific distress was high (IES scores >26). Mean psychopathology (SCL-90) scores were low, mean mood states (POMS) scores were moderate. Interval MSI–CRC was not related to psychological distress. High cancer specific distress was reported by 24% of patients diagnosed with CRC less than 12 months ago versus 39 and 35% by those diagnosed between 12 and 36 months and more than 36 months ago respectively. Distress was positively related to female gender (P = 0.04), religiousness (P = 0.01), low social support (P = 0.02) and difficulties with family communication (P < 0.001). Shortened time interval between CRC diagnosis and MSI-testing is not associated with higher psychological distress. Females, religious persons, those having low social support and those reporting difficulties communicating hereditary colorectal cancer with relatives are at higher risk for psychological distress.     

Second‐line cetuximab/irinotecan versus oxaliplatin/fluoropyrimidines for metastatic colorectal cancer with wild‐type KRAS

The goal of the present study was to compare the efficacy of the combination of cetuximab and irinotecan to the combination of oxaliplatin and fluoropyrimidines as second‐line chemotherapy in patients with irinotecan‐refractory and oxaliplatin‐naïve metastatic colorectal cancer (mCRC) harboring wild‐type KRAS. The study included 120 patients with mCRC who had progressed after irinotecan‐containing first‐line chemotherapy and were never treated with oxaliplatin; 40 patients with wild‐type KRAS were accrued prospectively in the experimental arm (arm A), and 80 patients accrued retrospectively were divided into control arms B (n = 46) and C (n = 34) according to KRAS genotype. Second‐line treatments consisted of cetuximab plus irinotecan for arm A, and oxaliplatin plus either 5‐fluorouracil (FOLFOX) or capecitabine (CapeOX) for the control arms. The median progression‐free survival (PFS) was 8.3, 5.8 and 3.9 months, for arms A, B and C, respectively, with statistical significance favoring arm A (P = 0.007). Differences in overall survival did not reach statistical significance (18.3 vs 12.6 vs 12.9, P = 0.138), although there was a trend toward longer overall survival in arm A. In terms of benefit from oxaliplatin‐containing regimens either as second‐line or third‐line therapy, the median PFS was 5.0 months in arms B and C as second‐line therapy, and 4.0 months in arm A as third‐line therapy, with no statistical significance (P = 0.385). Second‐line cetuximab plus irinotecan is a valid treatment strategy for mCRC patients with irinotecan‐refractory and oxaliplatin‐naïve tumors harboring wild‐type KRAS. Oxaliplatin‐containing chemotherapy resulted in equivalent PFS both as a second‐line and a third‐line therapy, enabling delay of the administration of FOLFOX and CapeOX until subsequent treatment cycles.     

Brain metastases from colorectal carcinoma: a description of 60 cases in a single Chinese cancer center

The incidence of brain metastasis (BM) from colorectal carcinoma (CRC) is increasing. The objectives of the present study were to explore the clinical characteristics and potential prognostic factors in CRC patients with BM. Between April 1991 and December 2010, all CRC patients treated in the Sun Yat-sen University Cancer Center were retrospectively reviewed and 60 patients were identified to have BM (36 males and 24 females). The association between patients and their tumor characteristics, treatment modality, and survival were statistically analyzed. The median age at diagnosis of BM was 62.5 years. Fifty-three patients (88.3%) developed extracranial metastases at diagnosis of BM. The cause of death was systemic disease in 19 patients and neurological disease in 23 patients. Brain metastases were primarily treated with either whole brain radiation therapy (WBRT; 15 patients), stereotactic radiosurgery (SRS; nine patients), or surgical resection (seven patients). Ten patients received WBRT and SRS, and 19 patients (31.7%) were treated with steroids alone. The median survival after diagnosis of BM was 8 months (95% confidence interval = 4.2–11.8 months). Recursive partitioning analysis (RPA) class, the number of brain lesions, and treatment modality type were significantly associated with survival. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. A low RPA class and a limited number of brain lesions may predict increased survival after therapy for CRC patients with BM.     

Salvage treatment with topotecan in patients with irinotecan-refractory small cell lung cancer

Purpose  Although the efficacy of topotecan as a second-line chemotherapy for small-cell lung cancer (SCLC) has been consistently demonstrated in phase II/III clinical trials, the choice of irinotecan as the first-line therapy prevented the use of evidence-based option. This pilot study was conducted to determine the activity and safety of topotecan in SCLC patients refractory to first-line therapy with irinotecan and platinum. Methods  Patients with primary refractory (no response, or progression during or ≤90 days after last chemotherapy) SCLC after treatment with a combination of irinotecan and platinum, received topotecan 1.5 mg/m² per day as a 30-min infusion daily for 5 days, every 3 weeks. Results  Of 17 eligible patients, ten patients were previously treated with irinotecan plus cisplatin and 7 were treated with irinotecan plus carboplatin. The median age was 68 years (range 44–75) and the median interval from the last chemotherapy was 50 days (range 21–89). A total of 33 chemotherapy cycles were delivered (median 2; range 1–5). All 17 patients discontinued therapy due to disease progression and 5 patients had progressive disease before second cycle. Toxic effects were mainly hematologic (grade ≥3 neutropenia in 65% of patients) and fatigue (grade 3 in 47%). In an intent-to-treat analysis, two (12%) patients had a confirmed partial response and two patients achieved stable disease. Median progression-free and overall survivals were 1.7 months (95% CI, 1.5–1.9) and 3.4 months (95% CI, 1.7–5.0), respectively. Conclusions  Topotecan monotherapy for patients with irinotecan-refractory SCLC does not appear highly active but the observation of some responses merits further study in patients with chemosensitive disease.     

Randomized multicenter phase II study comparing a combination of fluorouracil and folinic acid and alternating irinotecan and oxaliplatin with oxaliplatin and irinotecan in fluorouracil-pretreated metastatic colorectal cancer patients.

PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination. PATIENTS AND METHODS: Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m(2) followed by a 400-mg/m(2) 5-FU bolus injection, then a 600-mg/m(2) continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m(2) on day 1) and oxaliplatin (85 mg/m(2) on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) every 3 weeks. RESULTS: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred. CONCLUSION: The every-3-weeks OC combination is safe and active in advanced 5-FU-resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.     

A multiple-center phase II study of biweekly oxaliplatin and tegafur–uracil/leucovorin for chemonaive patients with advanced gastric cancer

Purpose  The current study assessed the efficacy and safety of biweekly oxaliplatin combining oral tegafur–uracil/leucovorin in treating chemonaive patients with advanced gastric cancer. Methods  Eligible patients were 18–75 years old, had stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0–2. Patients in the current study received 2-h i.v. infusion of oxaliplatin at a dose of 100 mg/m² after diluting in 500 mL 5% dextrose/water (dexan premedication), and 5-HT3 antagonist biweekly. Oral tegafur–uracil and leucovorin was given at a dose of 300 mg/m²/day and 60 mg/day three times daily from day 1 to 21, respectively, followed by a 1-week rest. Response assessment was based on the RECIST criteria and was performed every two courses. Toxicity was assessed according to NCI common toxicity criteria version 2. Results  From October 2003 to April 2006, 57 patients were evaluated (55 eligible) with a median age of 61 years (range 31–75). According to the assessment of response in 48 evaluable patients, partial response rate was 24/48 (50.0%) (95% CI: 35.23–64.73%) and stable disease was observed in 11 patients (22.92%), and diseased progressed in 13 patients (27.08%). Mean number of oxaliplatin cycles was 3 (0.5–6.5). Median time to progression was 177 days. Median overall survival was 318 days. Major-grade (III/IV) toxicities were diarrhea 25.5%, vomiting 16.5%, anemia 10.9%, numbness 12.7%, thrombocytopenia 7.3%, neutropenia 3.6% and leucopenia 1.8%. Conclusions  Biweekly, oxaliplatin combining oral tegafur–uracil/leucovorin in treating patients with advanced gastric cancer showed acceptable activity and manageable toxicity. This study was presented in part at the 7th International Conference of the Asian Clinical Oncology Society, September 14–28, 2006, Beijing, China.     

Taxane-based chemotherapy enhances response to neoadjuvant treatment for stage II and III breast cancer

The feasibility, safety, and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil (5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma (UGIA) are unknown. Seventy-three patients with gastric (GC; n = 22), pancreatic (PC; n = 28) or biliary cancer (BC; n = 23) were randomised to start with 45 mg/m² docetaxel or 180 mg/m² irinotecan combined with 5-FU/leucovorin every 2nd week. After every 2nd course, the patients were crossed over to the other combination. Treatment was given for a maximum of 12 courses. Quality-of-life (QoL) was evaluated during the first two months using the EORTC QLQ-C30. Eighteen patients (25%; GC 32%, PC 21%, BC 22%) demonstrated partial response (PR) and 21 (29%) had prolonged stable disease. Mean QoL scores were low at baseline. Twenty-three (32%) patients had improved QoL using a summary measure and 13 were stable. Median time to progression was 4.4 months and overall survival 8.2 months. The treatments were reasonably well tolerated. Grade 3–4 toxicities were slightly more common for the docetaxel combination. There were two treatment-related deaths. Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible, reasonably tolerable and appears active in advanced UGIA.     

Combination chemotherapy with cisplatin and irinotecan in patients with adenocarcinoma of the small intestine

Background  Small-bowel adenocarcinoma (SBA) is a rare tumor that has a poor response to chemotherapy and a poor prognosis. Treatment strategies for SBA have not been clearly established. Methods  All patients with SBA treated using a combination of cisplatin and irinotecan (IP) as first-line chemotherapy at the National Cancer Center Hospital in Japan between January 1999 and February 2007 were studied retrospectively. Results  Eight patients received IP as first-line chemotherapy. The median follow-up was 9.5 months (range, 4.2–37.5 months). The median number of cycles of IP was three (range, 1–5). The overall response rate (complete or partial response) was 12.5% (complete response, n = 0; partial response, n = 1). The disease control rate (complete or partial response or stable disease) was 75%. The median time to treatment failure was 4.5 months (95% confidence interval, 0.9–5.8 months), and overall survival was 17.3 months (range, 1.9–21.3 months). The most common adverse events were neutropenia and anorexia. Conclusion  IP combination chemotherapy may be an acceptable option for patients with SBA. Further studies are warranted to determine the optimal chemotherapeutic regimen for SBA.     

Stereotactic radiosurgery in the management of brain metastases from primary thyroid cancers

Patients with metastatic well-differentiated thyroid cancer have a generally favorable long-term outcome although multi-organ involvement is a known marker of poor prognosis. Brain metastases are rare, occurring in less than 1% of patients with thyroid cancer. Few patients have been managed with stereotactic radiosurgery (SRS). A retrospective database of 5,067 patients treated for brain metastases between 1985 and 2007 was generated from 11 institutions. Thyroid cancer patients were identified in this database and, when possible, additional information was obtained from further chart review. Patients were excluded if they had incomplete treatment or follow-up information. Two validated prognostic indices, Graded prognostic Assessment (GPA) and Recursive Partitioning Analysis (RPA), were calculated for each patient. The overall survival times were calculated by the Kaplan–Meier method. Twenty-three thyroid cancer patients were identified (51% male, 48% female). Median age was 63 years (range 20–81). Pathology of the primary thyroid disease was available for twelve patients; the majority were diagnosed with differentiated thyroid cancer (n = 9 papillary, n = 2 Hürthle cell; 92%) and one had medullary subtype (8%). Median time from diagnosis of primary disease to brain metastasis was 41.8 months (range 0–516). Fifteen (65%) patients underwent SRS as part of their initial treatment with a median number of lesions treated of 1.5 (range 1–9). The median follow-up time for living patients was 35.2 months. Overall median survival time was 20.8 months (40% alive at last follow-up) and 37.4 months for SRS-treated patients (P = NS). A poor Karnofsky performance status was predictive of worse outcome (P = 0.001). GPA and RPA did not provide additional prognostic information. In conclusion, patients treated with SRS for brain metastases from primary thyroid cancer have a favorable prognosis with an expected median survival greater than 3 years. It is unclear as to whether current prognostic indices are relevant to this patient population.     

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.     

Capecitabine plus oxaliplatin (xelox) in the treatment of chemotherapy-naive patients with metastatic colorectal cancer

Background Capecitabine and oxaliplatin are both synergistically active against metastatic colorectal cancer (MCRC). We evaluated our experience at two centers with capecitabine and oxaliplatin combination (XELOX) in previously untreated patients with MCRC. Patients and methods We reviewed medical records of 85 previously untreated patients with MCRC who received first-line XELOX regimen. Oxaliplatin was given at a dose of 130 mg/m² on day 1 in combination with capecitabine 1500 mg/m²/day on days 1–14 every 3 weeks. Results Seventy six of 85 patients were evaluated for response and toxicity. Patients with a follow up of less than 6 months were excluded from the study. Objective response rate was 46% including 8 complete responses (10.5%) and 27 partial responses (35.5%). Additionally, 20 patients (26.3%) had disease stabilization at least 3 months after the treatment. The patients were followed for a median 12.5 months (range 2–32). Median time to disease progression (TTP) was 11 months (range 2–27 months). Median overall survival (OS) time has not yet been reached. One-year survival rate was 66%. Toxicity was modest with infrequent grade 3–4 adverse effects. Conclusion XELOX is an active regimen against MCRC in the first-line setting with favorable toxicity profile. Our results appear to be comparable, if not superior, to the results of other reports of first-line XELOX therapy in respect to objective response rates, survival data, and safety profile. Convenience with oral administration of every 3-week schedule makes XELOX regimen a compelling therapeutic option in the treatment of first-line MCRC.     

Phase II study of paclitaxel combined with capecitabine as second-line treatment for advanced gastric carcinoma after failure of cisplatin-based regimens

Purpose  To determine the safety and the efficacy of paclitaxel and capecitabine as second-line combination chemotherapy after failure of platinum regimens in advanced gastric cancer. Methods  Patients with histologically proven gastric cancer and measurable metastatic disease received capecitabine 825 mg/m² twice daily (1,650 mg/m² per day) on days 1–14 and paclitaxel 175 mg/m² by intravenous infusion on day 1 every 3 weeks until disease progression or unacceptable toxicities. Results  Between June 2003 and October 2005, 26 patients, of median age 59 years (range 41–84 years) were included in the study and were treated by paclitaxel/capecitabine combination. Overall response rate was 34.6% (95%CI = 17.2–55.7%) with one complete response and 42.3% (95%CI = 17.2–55.7%) of patients achieved a stable disease. Median progression-free survival was 4.5 months (95%CI = 4–4.5 months). Median overall survival was 7.5 months (95%CI = 6–10 months). Cumulated overall survival including cisplatin regimens was 15.5 months (95%CI = 11–18 months). Grade 3/4 adverse events included alopecia (30.8%), neutropenia (11.5%), hand foot skin reaction (11.5%), neuropathy (11.5%), arthralgias (7.5%), and anemia (3.8%). Conclusions  Paclitaxel and capecitabine combination was safe and effective in advanced gastric cancer after failure of cisplatin regimens. The cumulated overall survival of 15.5 months suggests a particular interest of taxanes in second-line treatment after failure of platinum salts.     

Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741.

BACKGROUND: Fluorouracil (5-FU), oxaliplatin and irinotecan combinations improve time to tumor progression (TTP), objective response and overall survival (OS) in patients with metastatic colorectal cancer (MCRC). Here we identify and describe patients treated on Intergroup study N9741 who initially had inoperable MCRC, but who obtained sufficient chemotherapeutic benefit to allow removal of their metastatic disease. PATIENTS AND METHODS: Patient research records in study arms (A) irinotecan/5-FU/leucovorin (LV) (IFL, n = 264), (F) oxaliplatin/5-FU/LV (FOLFOX4, n = 267) and (G) oxaliplatin/irinotecan (IROX, n = 265) were reviewed. TTP and median OS were calculated. RESULTS: Twenty-four (3.3%) of 795 randomized patients underwent curative metastatic disease resection [hepatectomy, 16; radiofrequency-ablation (RFA), six; lung resection, two]. Twenty-two out of 24 (92%) resected patients received an oxaliplatin-based regimen (FOLFOX4, 11; IROX, 11). Seven patients (29.2%) remain disease-free; relapses occurred mainly in the resected organ. Median OS in resected patients is 42.4 months, and median TTP is 18.4 months. All six patients treated with RFA have recurred. Four out of five (80%) patients who received chemotherapy following resection are disease-free. CONCLUSIONS: Resection of metastatic disease after chemotherapy is possible in a small but important subset of patients with MCRC, particularly after receiving an oxaliplatin-based chemotherapy regimen, with encouraging OS and TTP observed in these highly selected patients.