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Marc Ychou

Publications and source records attributed to Marc Ychou.

35 records · Page 2Linked to original sources
PubMed2005

[Clinical Practice Guidelines 2004. Standards, Options and Recommendations for the management of patient with adenocarcinoma of the stomach: radiotherapy (therapeutic evaluation)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French regional cancer centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To elaborate clinical practice guidelines for patients with stomach adenocarcinoma. These recommendations cover the diagnosis, treatment and follow-up of these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. The Standards, Options and Recommendations are thus based on the best available evidence and expert agreement. RESULTS: This guidelines presents the synthesis of the data concerning the evaluation of the therapeutic ones. The main questions concern the type of gastrectomy to realize (Total Gastrectomy or gastrectomy subtotal), the extent of the lymphadenectomy (D2, D3 versus D1, D3, D2 versus D4) and the role of postoperative chemotherapy and adjuvant concomitant chemoradiotherapy.

Adenocarcinoma↗
PubMed2004

Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA) Gold 4 epitope and designed for radioimmunotherapy (RIT) of colorectal cancers.

BACKGROUND: Human monoclonal antibodies (MAbs) are needed for colon cancer radioimmunotherapy (RIT) to allow for repeated injections. Carcinoembryonic antigen (CEA) being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. METHODS: XenoMouse-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2kappa and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. RESULTS: Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2kappa and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2kappa and VG-IgM were determined to be 0.19 +/- 0.06 x 10(8) M(-1) and 1.30 +/- 0.06 x 10(8) M(-1), respectively, as compared with 0.61 +/- 0.05 x 10(8) M(-1) for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2kappa and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10(-7) M was needed to precipitate approximatively 1 ng 125I-rhCEA as compared with 10(-9) M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, 125I-VG-IgG2kappa demonstrated a high tumor uptake (25.4 +/- 7.3%ID/g), close to that of 131I-X4 (21.7 +/- 7.2%ID/g). At 72 h post-injection, 125I-VG-IgG2kappa was still concentrated in the tumor (28.4 +/- 11.0%ID/g) whereas the tumor concentration of 131I-X4 was significantly reduced (12.5 +/- 4.8%ID/g). At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of VG-IgM biodistribution was not possible in this mouse model in which IgM displays a very short half-life due to poly-Ig receptor expression in the liver. CONCLUSION: Our human anti-CEA IgG2kappa is a promising candidate for radioimmunotherapy in intact form, as F(ab')2 fragments, or as a bispecific antibody.

Animals↗
PubMed2004

ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases.

Overcoming drug resistance has become an important issue in cancer chemotherapy. Among all known mechanisms that confer resistance, active efflux of chemotherapeutic agents by proteins from the ATP-binding cassette family has been extensively reported. The aim of the present study was to determine the involvement of ABCG2 in resistance to SN38 (the active metabolite of irinotecan) in colorectal cancer. By progressive exposure to increasing concentrations of SN38, we isolated 2 resistant clones from the human colon carcinoma cell line HCT116. These clones were 6- and 53-fold more resistant to SN38 than the HCT116-derived sensitive clone. Topoisomerase I expression was unchanged in our resistant variants. The highest resistance level correlated with an ABCG2 amplification. This overexpression was associated with a marked decrease in the intracellular accumulation of SN38. The inhibition of ABCG2 function by Ko143 demonstrated that enhanced drug efflux from resistant cells was mediated by the activity of ABCG2 protein and confirmed that ABCG2 is directly involved in acquired resistance to SN38. Furthermore, we show, for the first time in clinical samples, that the ABCG2 mRNA content in hepatic metastases is higher after an irinotecan-based chemotherapy than in irinotecan-naive metastases. In conclusion, this study supports the potential involvement of ABCG2 in the development of irinotecan resistance in vivo.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2004

Gemcitabine and docetaxel as front-line chemotherapy in patients with carcinoma of an unknown primary site.

BACKGROUND: The current study was performed to evaluate the efficacy and toxicity of a noncisplatin-based chemotherapy regimen combining gemcitabine and docetaxel as front-line chemotherapy for patients with carcinoma of an unknown primary site. METHODS: Patients were to receive intravenous gemcitabine at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 and docetaxel at a dose of 75 mg/m2 over 1 hour on Day 8 in an outpatient setting. The schedule was repeated every 3 weeks for a maximum of 6 cycles. RESULTS: Thirty-five patients were assessable for response and survival. One complete and 13 partial responses were observed. The overall response rate was 40% (95% confidence interval, 28-52%). The median time to disease progression was 2 months (range, 1-4 months). The median overall survival time was 10 months (range, 0-32 months). Toxicity was reported to be manageable. CONCLUSIONS: The combination of gemcitabine and docetaxel was found to be active in patients with carcinomas of an unknown primary site. However, the overall outcome of these patients remains poor and novel treatment approaches are required.

Adult↗
PubMed2003

Individual 5-FU dose adaptation in metastatic colorectal cancer: results of a phase II study using a bimonthly pharmacokinetically intensified LV5FU2 regimen.

AIM: The aim of this phase II study was to determine the efficacy and tolerability of the bimonthly, pharmacokinetically intensified LV5FU2 regimen in the treatment of metastatic colorectal cancers. METHODS: A total of 53 patients (23% second-line; 25 male/28 female; mean age 67 years; WHO performance status 0 in 38, 1 in 10 and 2 in 5) were treated in cycle 1 with the standard LV5FU2 regimen (leucovorin 200 mg/m2 per day followed by a 5-FU bolus 400 mg/m2 per day and a 22-h 5-FU continuous infusion 600 mg/m2 per day for two consecutive days every 2 weeks), and the AUC in mg.h/l.m2 was calculated. For cycle 2, according to a predefined schedule depending on the cycle-1 AUC value, in the absence of grade 3 toxicity, the 5-FU infusion dose was increased by 150% for AUC < or =5, by 100% for AUC >5-10, by 50% for AUC >10-15, and by 25% for AUC >15-20. 5-FU plasma concentrations were determined using high-performance liquid chromatography. A Bayesian methodology was used to assess individual pharmacokinetic parameters using the NONMEM computer program. RESULTS: Among the 53 eligible patients, 87% (per-protocol population) received an increased dose in cycle 2 and 72% received the same dose. The median relative dose intensity was 1.28 (range 0.5-1.54) compared with the non-adapted theoretical total 5-FU dose. The objective response rate was 37% (95% CI 23-50%) in the intention-to-treat population and 47% (95% CI 29-65%) in the first-line per-protocol population. The median response duration was 10.4 months. The median progression-free survival (PFS) and overall survival (OS) were, respectively, 7 and 18.6 months. PFS and OS in first-line per-protocol patients were, respectively, 9.2 and 20 months. No deaths were attributed to toxicity of 5-FU despite the high doses administered. Of the 53 patients, 19% experienced gastrointestinal and 30% haematological grade 3/4 toxicities. Hand-foot syndrome was common but mild (grade 3 in one patient). CONCLUSIONS: This strategy could be compared in a phase III trial with the standard LV5FU2 regimen.

Adenocarcinoma↗
PubMed2003

Enhancement of radiation therapy by tumor necrosis factor alpha in human colon cancer using a bispecific antibody.

PURPOSE: To overcome the systemic side effects of tumor necrosis factor alpha (TNFalpha) injected i.v., we used a bispecific antibody (BAb) directed against carcinoembryonic antigen (CEA) and TNFalpha to target this cytokine in human CEA-expressing colorectal carcinoma treated simultaneously with radiation therapy (RT). METHODS, MATERIALS AND RESULTS: LS174T cell line was used to study the interaction of TNFalpha and radiation on clonogenic cytotoxicity. When TNFalpha (2500 U/mL) was added 12 h before RT, the surviving fraction at 2 Gy was 54% lower than that obtained with irradiation alone (0.23 vs. 0.42, respectively, p = 0.001). At 20%, 50%, or 70% survival, data points were within the envelope of additivity. Concerning in vivo experiments, RT as a single agent slowed tumor progression as compared with the control group (p = 0.027), whereas TNFalpha, BAb, or BAb + TNFalpha had no effect. BAb + TNFalpha + RT combination enhanced the delay for the tumor to reach 2000 mm(3) as compared with RT alone (p = 0.033, for BAb + TNFalpha + RT group vs. RT group). CONCLUSION: These results suggest that TNFalpha in combination with BAb and RT may be beneficial for the treatment of locally advanced colorectal cancer.

Adenocarcinoma↗
PubMed2003

Sensitive HPLC-fluorescence method for irinotecan and four major metabolites in human plasma and saliva: application to pharmacokinetic studies.

BACKGROUND: We developed gradient HPLC methods for quantification of the antimitotic drug irinotecan (CPT-11) and its four metabolites, SN-38, SN-38 G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC), and 7-ethyl-10-[4amino-1-piperidino]-carbonyloxycamptothecin (NPC), as the sum of the lactone and carboxylate forms, in human plasma and saliva. Camptothecin was used as internal standard. METHODS: The sample pretreatment involved protein precipitation with methanol-acetonitrile (50:50 by volume) followed by acidification with hydrochloric acid to convert the lactone ring-opened form into its lactone form, quantitatively. HPLC separation was performed on a Xterra RP18 column. The excitation wavelength was 370 nm, and the emission wavelength was set at 470 nm for the first 24 min and then at 534 nm for the next 4 min. The stabilities of irinotecan and its four metabolites in plasma, saliva, and acidic extracts were also investigated under various conditions. RESULTS: Assays were linear in the tested range of 0.5-1000 micro g/L. For the five analytes, limits of quantification were 0.5 micro g/L in both matrices. The interassay imprecision (as relative standard deviation) was 3.2-14% in plasma and 2.6-5.6% in saliva. Assay recoveries ranged from 92.8% to 111.2% for plasma and 100.1% to 104.1% for saliva. Mean extraction recovery from plasma or saliva was 90%. CONCLUSION: The developed assay can be used to determine pharmacokinetic parameters for CPT-11, SN-38, SN-38 G, APC, and NPC in plasma and saliva from patients with metastatic colorectal cancer.

Antineoplastic Agents, Phytogenic↗
PubMed2003

[External beam radiation therapy and interstitial brachytherapy in the treatment of anal canal carcinomas: a series of 70 patients].

This study is concerning 70 patients (57 female, 13 male) with an epidermoid carcinoma of the anal canal which were treated homogeneously with a combination of an external beam radiation therapy ((45 Gy in 25 fractions of 1.8 Gy for 5 weeks) and a brachytherapy with Iridium wires (15 to 20 Gy delivered to the gross residual disease). The N1 patients and the patients with tumors more than 4 cm in diameter received a chemotherapy also (5 FU and cisplatinum). The overall local control was obtained in 68 cases out of 70 (97.1%). 63 out of 70 patients (90%) are alive and locally controlled. 56 pts out of 70 (80%) did have a preserved anus, and a normal sphincterian function was preserved in 53 pts out of 70 (75.7%). 17 pts had a colostomy (3 without and 14 with an abdominoperineal resection). With the salvage perineal resection, 11 patients out of 12 local recurrences were definitely locally cured (91.7%). The 5-year overall survival is 91.4%. The 5-year disease-free survival is 90%. The 5-year survival with preserved anal sphincter is 80% and with preserved sphincterian function is 75.7%. Five patients died from cancer (3 deaths due to metastases, and only 2 due to a locoregional evolution). These results have been analysed regarding the literature data and demonstrated the curative role of external beam and brachytherapy, in localized tumors, the contribution of chemotherapy in advanced stages and the efficiency of secondary salvage surgery in local recurrences.

Adult↗
PubMed2003

[Radiotherapy and inhibitors of epidermal growth factor receptor: preclinical findings and preliminary clinical trials].

Recent studies have demonstrated that ionizing radiation activate existing cellular response pathways involving protein kinases. These pathways mediate the cytotoxic and cytoprotective responses of cell death and cell survival, respectively. Cytoprotective responses involve dominantly mitogen-activated protein kinase (MAPK) through radiation-induced activation of EGF receptors and may stimulate cell proliferation if radiation-induced damage is successfully repaired. Similarly, overexpression of EGF receptor family members or their activation by ligands expressed at normal levels may also confer radioresistance. Recent encouraging results indicate that EGF receptor inhibitors such as antibodies or small molecule tyrosine-kinase inhibitors may be effective radiosensitizers in tumors. Within the antibody class of EGF receptor inhibitors are monoclonal antibodies such as cetuximab and trastuzumab. These agents have a common target of the extracellular domain of the EGF receptor. Striking synergistic antitumor effects on human epidermoid and on adenocarcinoma cancer-cell xenografts have been observed when cetuximab treatment is combined with radiotherapy. Promising results have also been obtained from the first clinical trial with cetuximab and radiotherapy in squamous-cell carcinoma of the head and neck. Trastuzumab has been poorly studied in combination with radiotherapy but showed an increased radiosensitivity of HER2-overexpressing breast cancer cells as measured by in vitro colony-forming assays. The mechanism of radiosensitization appears to involve DNA repair. There are well over a dozen agents in the small molecule tyrosine-kinase inhibitor category but the preclinical studies in combination with radiotherapy exist only for ZD1839 and CI1033. Preliminary studies confirm the capacity of ZD1839 and radiotherapy to produce a highly significant increase in tumor growth inhibition when compared to treatment with either modality alone. Another member of the quinazoline class of small molecule tyrosine-kinase inhibitors (CI1033) has recently been examined for its impact in conjunction with radiation in a series of HER-overexpressing breast cancer cell lines. This molecule inhibits tyrosine-kinase activity in all four members of the HER family, and preclinical studies showed a synergistic interaction of CI1033 with ionizing radiation. Finally, EGF receptor family member inhibitors may themselves be effective radiosensitizers and their use in future clinical investigations are based on a solid radiobiological rational.

Animals↗
PubMed2002

Drug specific resistance to oxaliplatin is associated with apoptosis defect in a cellular model of colon carcinoma.

To investigate acquired resistance to oxaliplatin, we selected two resistant clones from the HCT116 cell line. We found that the resistant phenotype was associated with resistance to oxaliplatin-induced apoptosis as demonstrated by FACS analysis and by Western blotting of caspase 3 activation. In addition, the resistant phenotype showed a concomitant resistance to lonidamine and arsenic trioxide which are inducers of mitochondrial apoptosis. Furthermore, a complete loss of Bax expression due to a frameshift mutation was observed in the most resistant clone. Taken together, these findings suggest that altered mitochondrial-mediated apoptosis could play a role in oxaliplatin resistance.

Antineoplastic Agents↗
PubMed2002

Alternative bimonthly cycles of doxorubicin, cyclophosphamide, and etoposide, cisplatin with hematopoietic growth factor support in patients with carcinoma of unknown primary site.

BACKGROUND: Because carcinomas of unknown primary origin are highly malignant tumors with a bad prognosis (median survival, 6-12 months) and no current optimal therapy, the authors designed a prospective dose-dense chemotherapy regimen with the objective of improving the results observed in patients who receive conventional treatment. METHODS: Eighty-two patients received alternative bimonthly cycles of doxorubicin 50 mg/m(2) with cyclophosphamide 1000 mg/m(2) (AC) and etoposide 300 mg/m(2) with cisplatin 100 mg/m(2) (EP). Cycles were given at 2-week intervals with granulocyte-macrophage-stimulating factor support (5 microg/kg per day) from Day 4 to Day 10. Patients without measurable lesions were included, because the major end point was survival. RESULTS: The median number of alternative cycles of AC and EP was 4 cycles (range, 1-12 cycles). An objective response was observed in 24 of 62 patients (39%; 95% confidence interval, 30-48%) with measurable lesions, including 6 patients who achieved a complete response. Among 20 patients with nonmeasurable disease, 9 patients (45%) had no evidence of progressive disease at the end of chemotherapy. The overall median survival of 82 patients was 10 months, with 5 patients surviving clinically disease free at 17 months, 29 months, 45 months, 64 months, and 70 months after the end of treatment. Myelosuppression was the most common toxicity. Two toxic deaths occurred. CONCLUSIONS: Using these doses and schedules, a dose-dense chemotherapy regimen did not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with news drugs will be required.

Adult↗
PubMed2002

Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil and cisplatin.

INTRODUCTION: Adenocarcinoma of the pancreas remains one of the most difficult malignancies to treat. Its incidence has steadily increased over the past four decades, and its prognosis is still dismal. AIM To assess tumor control and the palliative benefit of 5-fluorouracil (5-FU), cisplatin (CDDP), and radiotherapy in patients with advanced pancreatic cancer. METHODOLOGY: Systemic chemotherapy consisted of 5-FU (600 mg/m ), given as a 22-hour infusion on days 1 to 5, and CDDP (100 mg/m ), given as a 90-minute infusion on day 2. Treatment courses were repeated identically on day 21. Radiotherapy was delivered using megavolt irradiation of 25-MV photons with a two- or four-field isocentric technique. RESULTS: Twenty-seven patients were treated with this radiochemotherapy (RCT). Twenty-one patients (78%) completed initial treatment. The median dose of radiation therapy delivered was 42.5 Gy. At the time of evaluation (1 month after the end of the RCT), no grade 4 (WHO) toxicity was observed; 12 patients had improved or stable body weight; pain was improved for 20 patients, with 11 experiencing no pain; and analgesic consumption decreased for 18 patients, of whom 11 stopped intake. The clinical benefit response was 7/27 (26%). Median survival and time to progression were, respectively, 9 and 4.4 months. CONCLUSION: This RCT regimen had a good impact on clinical benefit in locally advanced pancreatic carcinoma, without severe side effects.

Adenocarcinoma↗
PubMed2002

[Gemcitabine and ionizing radiations: radiosensitization or radio-chemotherapy combination].

Gemcitabine is a pyrimidine analog which has demonstrated antitumoral activity in a variety of solid tumors including bladder, non-small cell lung and pancreatic cancers. Gemcitabine is a potent radiosensitizer of human tumor cells. This review summarizes preclinical studies designed to elucidate the mechanism of action of gemcitabine with ionizing radiation. Phase I-II ongoing trials of combination of radiation therapy and gemcitabine are trying to determine the optimal dose and schedule which could be used in daily clinical activity. The mechanism of radiosensitization is thought to be simultaneously gemcitabine-induced dATP (deoxyadenosine triphosphate) depletion and cell cycle redistribution into the S phase. Although there are no real study which has proven supra-additive combination, the recent acute side effects in several clinical studies oblige physicists to determine with precision the maximum tolerated dose of gemcitabine in association with ionizing radiation. Radiosensitization conditions can be obtained either with a long exposition to a low concentration or a short exposition to a high concentration. Radiation sensitivity begin to be detected four hours after treatment for 48 hours. A dose about 100 mg/m2/week of gemcitabine could be used with radiation therapy according to recent phase I results. This limiting dose is approaching to a radiosensitization context where the effect of one agent is increased by another agent which is inactive or poorly active for the effect under consideration. In this type of regimen, the two modalities do interact with a frequent inhibition of recovery from potentially lethal damage and a probably increase of late side effects of radiation therapy. In contrast, radio-chemotherapy combination is used for a therapeutic advantage when the drug by itself is active against the tumor but does not enhance late side effects of radiation on the critical normal tissues within the irradiated volume. Gemcitabine surely is a strong radiosensitizer even at low doses with future extended combined modality therapeutic indications. The ultimate goal of combined treatments should be an increased therapeutic ratio.

Adenosine Triphosphate↗
PubMed2002

[Gemcitabine and pancreatic cancer].

The late diagnosis of pancreatic cancer, at a locally advanced and metastatic stage explains in part its poor prognosis. In this situation, three phase II trials with gemcitabine, a synthetic analogue of deoxycytidine, yielded some interesting results in terms of tolerance and efficiency. A new concept has also been depicted: the clinical benefit (defined by the level of pain, the consumption of analgesics and the general condition of the patient). These trials led to the realization of a randomized phase III study including 126 patients. The study compared the use of gemcitabine, in monotherapy, with fluoro-uracil (5FU), the standard form of treatment. There was evidence of clinical benefit in 23.8% of the patients treated with gemcitabine compared to only 4.8% of those receiving 5FU. The median and the overall survival at one year were significantly higher for the patients treated with gemcitabine (5.65 months and 18% respectively, versus 4.41 months and 2% for 5FU). The tolerance profile of gemcitabine was favourable. These have been confirmed by a large compassionate study undertaken in the United States, led by Storniolo, with more than 3,000 patients. Used in monotherapy, gemcitabine thus obtained authorization in 1996 to be released in the United States and in 1998 in Europe, to be used in the case of locally advanced or metastatic adenocarcinoma of the pancreas as first line chemotherapy. The administration regimen is 1,000 mg/m2 once a week (30 minutes i.v. infusion), for 7 weeks out of 8, then 3 weeks out of 4 in consecutive cycles. It is currently considered as the standard chemotherapy in this situation. Trials have been carried out to optimize the scheme for the administration of gemcitabine by lengthening its perfusion time. Current studies are now also being directed towards an association between gemcitabine and other cytotoxics, like cisplatinum or oxaliplatin.

Adenocarcinoma↗
PubMedDate not supplied

Gemcitabine and docetaxel after failure of cisplatin-based chemotherapy in patients with carcinoma of unknown primary site.

BACKGROUND: The prognosis of patients with carcinoma of unknown primary remains poor with an expected median survival of 6 to 12 months. We evaluated the activity of a chemotherapy regimen combining gemcitabine and docetaxel in patients who primarily failed cisplatin-based chemotherapy. PATIENTS AND METHODS: Fifteen patients received cycles of gemcitabine 1,000 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 every 3 weeks. RESULTS: The median number of cycles per patient was 3. Overall toxicity was moderate. Four partial responses were observed among 14 patients with measurable disease. The median survival was 8 months from start of therapy and 23 months from diagnosis. CONCLUSION: These results were obtained in a small series of selected patients and require further confirmation in the front-line management of the disease.

Adenocarcinoma↗
PubMedDate not supplied

Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial).

BACKGROUND: The objective of this phase III study was to compare the safety and efficacy of FLP (modulation of 5-FU (Fluorouracil) by folinic acid or leucovorin (LV) and cisplatin vs. FP (5-FU combined with Cisplatin) as a first line chemotherapy in advanced oesophageal, gastric and pancreatic cancer. PATIENTS AND METHODS: 232 patients with measurable lesions were randomised to receive at the first cycle either FP (arm A: 5-FU 800 mg/m2/d in continuous infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2), or FLP (arm B: LV, 100 mg/m2/d in bolus 5 days, followed by 5-FU 350 mg/m2/d in 1 h infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2). In case of no grade 3-4 haematological and diarrhoea toxicity, the dose of 5-FU was increased to 1000 mg/m2/d and 400 mg/m2/d in the two arms respectively, for the subsequent cycles until disease progression. RESULTS: The distribution of primary tumours was: 19 squamous cell carcinoma of the oesophagus, 19 oesophageal adenocarcinoma, 91 gastric and 97 pancreatic adenocarcinoma. Safety remained acceptable and comparable in the two arms except for the severe grade 3-4 mucositis, which was lower in arm B (4.5 vs. 16.4%, p < 0.009). Efficacy in terms of tumour response and survival was similar in the two arms, showing an objective response rate (after external review) of 18.6% (95% confidence interval (CI) 11.4-25.8%) in arm A vs. 15% (95% CI 8.5-21.6%) in arm B, an overall median survival of 24 weeks in arm A vs. 24.7 in arm B (p = 0.83) and a progression-free median survival of 12.4 weeks vs. 12.1 in arms A and B, respectively (p = 0.91). CONCLUSION: The FLP regimen is substantially equivalent to FP in terms of safety and quality of life, as well as for antitumour efficacy in these carcinomas; the only slight advantage of FLP in this study concerns mucositis. Based on these results, FLP could be used as an alternative to FP when appropriate.

Adult↗