Folinic Acid, Fluorouracil, Oxaliplatin Research Articles

Evaluation of Stages, Treatment Protocols, and Outcomes of Colorectal Cancer among West Bank Patients.

Background: Colorectal cancer (CRC) is the second most widespread cancer among Palestinian patients. As cancer care improves in hospitals across the West Bank, services like palliative care, targeted therapy, bone marrow transplantation, and individualized therapy are still limited. This study aimed to assess the CRC stages, treatment protocols, and survival rates of patients in the West Bank. Methodology: This retrospective study collected data from the medical records of Al-Najah University Hospital (NUH), which specializes in the care of cancer patients. Patients with confirmed CRC (stages I-IV) undergoing surgical or medical treatment were included in the study. Data collection was standardized by using a data collection form to gather information from the medical records included in the study. All statistical analyses were performed using SPSS (version v27), and survival was assessed using a regression analysis of the number of days from the time of diagnosis to the most recent visit against the type of treatment (e.g., surgery, chemotherapy, radiotherapy). Results: A sample of 252 patients with CRC from NUH was collected, including 143 males and 109 females aged between 27 and 86 years, with the average age being 60.6 ± 11.4 years. The sample included 183 patients (72.6%) diagnosed with colon cancer only, 29 patients (11.5%) diagnosed with rectal cancer only, and 40 patients (15.9%) diagnosed with both. Diagnosis took place at CRC stage I for 3 patients (1.2%), stage II for 33 patients (13.1%), stage III for 57 patients (22.6%), and stage IV for 159 patients (63.1%). Surgery was the most prevailing mode of treatment for 230 patients (91.3%), while 227 patients (90.1%) received chemotherapy treatment, and 38 patients (15.1%) received radiotherapy. Of the 252 patients, 40 patients (15.8%) received FOLFOX (i.e., folinic acid, fluorouracil, oxaliplatin), and 25 patients (9.9%) received FOLFIRI (i.e., folinic acid, fluorouracil, irinotecan), while the 187 remaining patients (74.2%) were treated with capecitabine, oxaliplatin, bevacizumab, cetuximab, regorafenib, cisplatin, etoposide, gemcitabine, or a combination thereof. The sample was categorized into six outcomes: (1) death, (2) cure, (3) disease progression, (4) disease recurrence, (5) under-treatment, and (6) unknown. Mortality was high, with 104 patients (41.3%) dying within a short time after diagnosis, and may have been attributable to delayed diagnosis. Surgical treatment had a positive impact on increasing the survival years, and it was significant (p = 0.033). Conclusions: A high percentage of patients were diagnosed in advanced CRC stages. The treatment modes were adopted from general international guidelines; however, the cure rates were low, and mortality was high. More studies need to be undertaken to investigate the actual application of chemotherapy protocols, and survival would benefit from the involvement of clinical pharmacists in the chemotherapy protocol selection, dosing, frequency, and follow-up. The present study advocates for greater public awareness of CRC and attests to the merits of screening by primary care professionals, which can help to avoid this serious illness and to promote a better prognosis.

LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study.

Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM. Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS. We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively. Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

Tumor Vascular Microenvironment of Colorectal Hepatic Metastasis and Chemotherapy Response.

The tumor vascular microenvironment has an important role in tumor progression and metastasis. The objective of this study was to assess the significance of metastatic hepatic tumor vascular microenvironment in relation to the response to systemic fluorouracil-based chemotherapy [folinic acid/fluorouracil/oxaliplatin (FOLFOX) or folinic acid/fluorouracil/irinotecan (FOLFIRI)]. A total of 48 consecutive patients with colorectal cancer (CRC) with hepatic metastasis were retrospectively reviewed, and factors such as metastatic tumor vascular microenvironment, chemotherapy response and hepatic resection, were analyzed. Tumor angiogenesis was microscopically evaluated by microvessel density (MVD) in sections stained immunochemically with antibody to CD34 in patients with hepatic resection. Angiogenesis in the tumor microenvironment in association with ring enhancement (RE) on computed tomography (CT) was also examined. Microscopic examination revealed that peripheral RE on CT of the metastatic tumor was associated with tumor angiogenesis by MVD. The overall response rate after six courses of first-line chemotherapy for liver metastasis with RE on CT was 64% (23/36), whereas the response rate for those without RE was 25% (3/12), which was significantly lower, although the survival of patients with RE-positive and RE-negative tumors did not differ significantly. Peripheral RE of metastatic hepatic tumor on CT was associated with angiogenesis in the tumor microenvironment and higher chemotherapy response.

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

The UPMC Hillman Cancer Center Approach to the Management of Colorectal Cancer During the COVID-19 Pandemic Era

Definitive re-irradiation of locally recurrent esophageal cancer after trimodality therapy in patients with a poor performance status.

There are few treatment guidelines for locally recurrent esophageal cancer after trimodality treatment (pre-operative chemoradiation followed by surgery) in patients with a poor performance status. The purpose of this single institutional, retrospective study was to evaluate the clinical outcomes and toxicities of definitive-intent re-irradiation for patients with recurrent esophageal cancer with a poor performance status [ECOG (Eastern Cooperative Oncology Group) ≥2]. Seven patients were identified with a median age of 74 years (range, 61-81 years). Four patients were ECOG 2 and three patients were ECOG 3. The median follow-up time after re-irradiation was 49 months. The median interval between initial radiotherapy and re-treatment was 32 months. Six patients received concurrent chemotherapy [carboplatin + paclitaxel in three patients; folinic acid, fluorouracil, oxaliplatin (FOLFOX) + 5-fluorouracil in one patient; FOLFOX in one patient, and capecitabine in one patient]. At the last follow-up, the six patients who underwent concurrent chemotherapy had stable disease (86%), while the one who did not receive chemotherapy progressed (14%). Two patients developed metastases. Three patients developed acute (<6 months) grade 4 toxicities (dysphagia, anemia, esophagitis). There were no early deaths attributable to treatment. Late toxicities (>6 months) were limited to grades 1 and 2 dysphagia and pneumonitis in four patients. In conclusion, definitive re-irradiation of recurrent esophageal cancer in patients with a poor performance status appears to be safe with acceptable acute toxicity and late complications. It also appears to result in durable local control when combined with chemotherapy, albeit with a small number of patients and limited follow-up.

Impact of Genomic Mutation and Timing of Y90 Radioembolization in Colorectal Liver Metastases.

To investigate timing of Yttrium-90 radioembolization (Y90) during treatment course, genomics, and other clinical factors as predictors of overall survival (OS) in colorectal liver metastasis (CRLM) that have progressed on at least one line of chemotherapy. This was a retrospective study from 2013 to 2018 of patients with CRLM and genomic analysis prior to Y90 at a multihospital tertiary referral center. OS from liver metastasis diagnosis and predictors of OS were analyzed using Kaplan-Meier estimation with log-rank and Cox regression analyses. Overall, 58 patients with CRLM who progressed on at least one line of chemotherapy who had genomic analysis prior to Y90 were identified. Median OS after hepatic metastasis was 29.9months. Of these, 16 (28%) patients received Y90 after failure of the first-line systemic chemotherapy. There was significantly prolonged OS in patients receiving Y90 immediately following failure of the first-line chemotherapy folinic acid, fluorouracil, oxaliplatin ((FOLFOX) ± bevacizumab) versus following multiple lines of chemotherapy (median OS of 46.3 vs. 26.6months, P = 0.005). The presence of genetic mutation in tumor, MAPK pathway wild type, left-sided primary tumor, low MELD score, and non-diffuse unilobar disease were also found to be predictors prolonged survival on log-rank analysis (P's < 0.05). On multivariate analysis, receiving Y90 after failure of the first line of chemotherapy, low baseline MELD score, and baseline ECOG performance score of 0 were all found to be independent predictors of prolonged OS from the time of metastatic disease diagnosis (P's < 0.05). In patients with CRLM, receiving Y90 after failing the first line of chemotherapy, lack of genetic mutation, low MELD score, and lower tumor burden appear to be independent predictors of prolonged OS. Level 4, case-control study.

Changes in Body Composition During Adjuvant FOLFOX Chemotherapy and Overall Survival in Non-Metastatic Colon Cancer

The impact of longitudinal anthropometric changes during adjuvant chemotherapy on long-term survival in non-metastatic colon cancer is unclear. Herein, we analyzed the prognostic significance of computed tomography (CT)-measured body composition changes in colon cancer patients who underwent surgery followed by adjuvant FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) chemotherapy. Data of 167 patients with stage III or high-risk stage II colon cancer were analyzed. Skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral fat index (VFI), subcutaneous fat index (SFI), and total fat index (TFI) changes during chemotherapy were calculated using preoperative and postchemotherapy CT image data. The Cox proportional hazard model was used to determine the correlation between changes in anthropometric values and overall survival (OS). The median changes (%) in SMI, SMR, VFI, SFI, and TFI over 210 days during chemotherapy were 8.7% (p < 0.001), 3.4% (p = 0.001), −19% (p < 0.001), −3.4% (p = 0.936), and −11.9% (p < 0.001), respectively. Cut-off values of changes in SMI (skeletal muscle index change, SMIC) and SMR (skeletal muscle radiodensity change, SMRC) were defined at −2% and −2 Hounsfield units (HU) respectively, whereas those of changes in VFI (visceral fat index change, VFIC), SFI (subcutaneous fat index change, SFIC), and TFI (total fat index change, TFIC) were based on values that provided the largest χ2 on the Mantel–Cox test. Multivariable analysis revealed that low SMR measured on a postchemotherapy CT scan (hazard ratio, HR: 0.32, 95% confidence interval, CI: 0.15–0.70, p = 0.004) and visceral fat loss of at least 46.57% (HR: 0.31, 95% CI: 0.14–0.69, p = 0.004) were independent poor prognostic factors for OS. Severe visceral fat loss during FOLFOX chemotherapy and low skeletal muscle radiodensity measured on postchemotherapy CT scans are associated with poor OS in stage III and high-risk stage II colon cancer patients.

Primary gastric adenosquamous carcinoma: a case report and literature review

Abstract Primary gastric adenosquamous carcinoma (GASC) is exceedingly rare. It accounts for less than 1% of all gastric cancers. In this report, we describe our pathological findings along with a review of the literature to improve our understanding of the disease and reduce misdiagnosis, as well as to provide evidence for its treatment and prognosis. A 49-year-old male patient was admitted to our hospital (Dalian Municipal Central Hospital, Dalian, China) with a complaint of epigastric pain that had persisted for half a month. Physical examination, regular laboratory blood tests, and computed tomography revealed no obvious abnormalities. Gastroscopy revealed ulcers in the lower part of the stomach, and pathological assessment revealed adenocarcinoma. Radical gastrectomy was performed, and the folinic acid, fluorouracil, oxaliplatin (FOLFOX) chemotherapy regimen was administered postoperatively. Pathological assessment of the mass revealed a protruding tumor measuring 1.5 × 1.5 × 0.7 cm in the lower part of the stomach. The tumor infiltrated through the full wall of the stomach. This was confirmed by immunohistochemical (IHC) staining for cytokeratin (CK) (+), villin (-), p63 (++), and high-molecular-weight CK (+++). The patient remains alive with no recurrence more than seven years after surgery. Primary GASC is a rare malignant neoplasm. The diagnostic criteria for GASC mainly depend on the clinical, radiographic, and histopathological findings. Pathological assessment and IHC staining can be utilized to confirm the diagnosis. Radical gastrectomy plus postoperative chemotherapy containing the FOLFOX regimen is effective for treating GASC and might contribute to long-term survival.

Network meta-analysis of the efficacy of first-line chemotherapy regimens in patients with advanced colorectal cancer.

This network meta-analysis compared the short-term and long-term efficacies of first-line chemotherapy regimens in patients with advanced colorectal cancer (CRC). The 10 regimens included folinic acid + 5-fluorouracil + oxaliplatin (FOLFOX), folinic acid + 5-fluorouracil + irinotecan (FOLFIRI), folinic acid + 5-fluorouracil + gemcitabine (FFG), folinic acid + 5-fluorouracil + trimetrexate (FFT), folinic acid + 5-fluorouracil (FF), irinotecan + oxaliplatin (IROX), raltitrexed + oxaliplatin (TOMOX), folinic acid + tegafur-uracil (FTU), raltitrexed, and capecitabine. Electronic searches were performed in the Cochrane Library, PubMed and Embase databases from inception to June 2017. Network meta-analysis combined direct and indirect evidence to obtain odds ratios (ORs) and surface under the cumulative ranking curves (SUCRA) of different chemotherapy regimens for advanced CRC. Fourteen randomized controlled trails (RCTs) covering 4,383 patients with advanced CRC were included. The results revealed that FOLFOX, FOLFIRI, IROX, and TOMOX all showed higher overall response rates (ORRs) than FF or raltitrexed. Compared with raltitrexed, the aforementioned four regimens also had higher 1-year progression-free survival (PFS) rates. In addition, FOLFOX and FOLFIRI exhibited higher disease control rates (DCRs) and 1-year PFS rates than FF or raltitrexed. Cluster analysis revealed that FOLFOX, FOLFIRI, and TOMOX had better short-term and long-term efficacies. These findings suggest FOLFOX, FOLFIRI, and TOMOX are superior to other regimens for advanced CRC. These three regimens are therefore recommended for clinical treatment of advanced CRC.

Relationship Between Metformin Use and Recurrence and Survival in Patients With Resected Stage III Colon Cancer Receiving Adjuvant Chemotherapy: Results From North Central Cancer Treatment Group N0147 (Alliance).

Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1-5, 6-10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age. Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use. The present study did not find any relationship between metformin use or its duration and disease-free survival, time to recurrence, and overall survival in a large cohort of patients with resected stage III colon cancer receiving adjuvant FOLFOX (folinic acid, fluorouracil, oxaliplatin)-based chemotherapy. This relationship was not modified by KRAS or BRAF mutation or DNA mismatch repair status. Metformin use did not increase or decrease the likelihood of chemotherapy-related grade 3 or higher adverse events.

Differential Therapeutic Effects of Anti–VEGF-A Antibody in Different Tumor Models: Implications for Choosing Appropriate Tumor Models for Drug Testing

We previously reported that the host response to certain chemotherapies can induce primary tumor regrowth, angiogenesis, and even metastases in mice, but the possible impact of anti-VEGF-A therapy in this context has not been fully explored. We, therefore, used combinations of anti-VEGF-A with chemotherapy on various tumor models in mice, including primary tumors, experimental lung metastases, and spontaneous lung metastases of 4T1-breast and CT26-colon murine cancer cell lines. Our results show that a combined treatment with anti-VEGF-A and folinic acid/5-fluorouracil/oxaliplatin (FOLFOX) but not with anti-VEGF-A and gemcitabine/cisplatinum (Gem/CDDP) enhances the treatment outcome partly due to reduced angiogenesis, in both primary tumors and experimental lung metastases models. However, neither treatment group exhibited an improved treatment outcome in the spontaneous lung metastases model, nor were changes in endothelial cell numbers found at metastatic sites. As chemotherapy has recently been shown to induce tumor cell invasion, we tested the invasion properties of tumor cells when exposed to plasma from FOLFOX-treated mice or patients with cancer. While plasma from FOLFOX-treated mice or patients induced invasion properties of tumor cells, the combination of anti-VEGF-A and FOLFOX abrogated these effects, despite the reduced plasma VEGF-A levels detected in FOLFOX-treated mice. These results suggest that the therapeutic impact of antiangiogenic drugs varies in different tumor models, and that anti-VEGF-A therapy can block the invasion properties of tumor cells in response to chemotherapy. These results may implicate an additional therapeutic role for anti-VEGF-A when combined with chemotherapy.

Individual Fluorouracil Dose Adjustment in FOLFOX Based on Pharmacokinetic Follow-Up Compared With Conventional Body-Area-Surface Dosing: A Phase II, Proof-of-Concept Study

To compare the efficacy and safety of pharmacokinetically (PK) guided fluorouracil (5-FU) dose adjustment vs. standard body-surface-area (BSA) dosing in a FOLFOX (folinic acid, fluorouracil, oxaliplatin) regimen in metastatic colorectal cancer (mCRC). A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy. The comparison arm consisted of 39 patients, and these patients were also treated with FOLFOX with 5-FU by BSA. For the PK-adjusted arm 5-FU was monitored during infusion, and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range (5-FU(ODPM Protocol)). The objective response rate was 69.7% in the PK-adjusted arm, and median overall survival and median progression-free survival were 28 and 16 months, respectively. In the traditional patients who received BSA dosage, objective response rate was 46%, and overall survival and progression-free survival were 22 and 10 months, respectively. Grade 3/4 toxicity was 1.7% for diarrhea, 0.8% for mucositis, and 18% for neutropenia in the dose-monitored group; they were 12%, 15%, and 25%, respectively, in the BSA group. Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing. Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC.

Prospective evaluation of the incidence of delayed nausea and vomiting in patients with colorectal cancer receiving oxaliplatin-based chemotherapy

9645 Background: Oxaliplatin (OX) is a platinum compound commonly used in colorectal cancer. The emetogenic potential of OX has not been well characterized despite reports of frequent nausea (N) and vomiting/retching (V) in phase I and II studies. Platinum compounds such as cisplatin and carboplatin have a well defined ability to cause delayed (> 24 hours post chemotherapy) NV in the absence of antiemetic prophylaxis. There is no information available on the potential for OX to produce delayed NV.This trial sought to prospectively determine the frequency of delayed N and V with OX-based chemotherapy following day 1 prophylaxis with a 5-HT3 antagonist (5-HT3A) and dexamethasone (DEX). Methods: Eligibility: Pts ≥ age 18 with colon cancer receiving OX (85–100mg/m2) as part of a standard FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) regimen for the first time. Performance status: 0–2. Antiemetic treatment: 5-HT3A (ondansetron, dolasetron, or granisetron but not palonosetron) at an approved dose and DEX 20mg PO/IV on day 1 prior to OX infusion. No routine prophylaxis for delayed N/V was given. Episodes of V, N, and use of rescue antiemetics were recorded in patient-completed diaries. Four point (none, mild, moderate, severe) categorical scales were used to assess N. Study period: 120 hours after OX administration. Definitions: complete response (CR) - no V and no use of rescue antiemetics (RA); complete control (CC) - no V, no N and no RA. Results: Pts: 36; evaluable 35; median age: 68 (48–85); M/F 46%/54%. History of moderate - heavy ethanol use: 8 pts (23%). Acute CR: 91% (32/35); Delayed CR: 51% (18/35); Delayed CC: 40% (14/35); Overall CR (0–120 hrs): 51% (18/35); Overall CC: 37% (13/35). Median time to first emesis/first rescue: 57 hrs/47 hrs. Conclusions: The use of a single dose of a 5-HT3A and DEX prior to OX results in excellent control of emesis (CR - 91%) during the 24 hours after chemotherapy. However, without further antiemetic treatment, complete response rate in the delayed period (hours 24 - 120) decreased to 51%. In addition, a majority of pts (57%) noted delayed N, with N of moderate to severe intensity in 9 (26%) pts. This study supports the need for routine antiemetic prophylaxis for delayed N and V following OX-based chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis

IFLUX for advanced bowel cancer

IFLUX, a chemotherapy regimen that combines irinotecan, 5-fl uorodeoxyuridine (FUdR), and folinic acid, might increase the median survival of patients with advanced colorectal cancer (Anticancer Drugs, 2007; 18: 955–61). In a phase II study of IFLUX, Bach Ardalan (University of Miami, FL, USA) and colleagues report that median patient survival was 31·3 months (95% CI 20·9– 38·0); in comparison, median survival with the widely used regimen of folinic acid, fl uorouracil, oxaliplatin (FOLFOX) is 19·5 months. Fluorouracil kills tumours partly through its activation, via FUdR, to fl uorodeoxyuridine monophosphate. This inhibits thymidylate synthase, which causes DNA damage and cell death. “Fluorouracil’s conversion to FUdR requires the addition of a deoxyribose sugar, which is often rate-limiting in cancer cells”, explains Ardalan, “so giving FUdR should bypass the ratelimiting step in fl uorouracil activation”. 38 patients with untreated, advan ced colorectal cancer received fi ve 6-week cycles (on average) of IFLUX. Each cycle comprised four weekly intravenous infusions of 110 mg/m irinotecan followed by a 24 h continuous intravenous infusion of 120 mg/kg FUdR and 500 mg/m folinic acid, and 2 weeks’ rest. Median time to tumour progression was 11·5 months (6·8–12·9). IFLUX was well-tolerated; toxic eff ects included vomiting (24%) and diarrhoea (16%). “Although this is a small study, it’s exciting to see the survival fi gures reported here”, comments Anne Thomas (University of Leicester, Leicester, UK). “However, I think it’s unlikely that the average patient with colorectal cancer could tolerate the toxicity associated with this regimen, which might also make it diffi cult to combine IFLUX with targeted agents. We await with interest the outcome of a phase II study combining IFLUX with bevacizumab that Ardalan is currently recruiting to.” Initial toxicity studies, notes Ardalan, indicate that this combination is acceptable to patients.