A phase I–II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer

Aschele, C.; Friso, Maria Luisa; Pucciarelli, Salvatore; Lonardi, Sara; Sartor, Luigi; Fabris, G.; Urso, Emanuele Damiano Luca; Bianco, Paola Del; Sotti, Guido; Lise, Mario; Monfardini, S.

doi:10.1093/annonc/mdi212

Cited by 133 publications

(74 citation statements)

References 33 publications

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“…The incidence of diarrhea was greater than that observed in our phase I-II study in the preoperative treatment of locally advanced rectal cancer [4]. We can argue that the combination of malnourishment, smoke and alcohol abuse may make the intestinal mucosa more sensitive to treatment damage, since gastrointestinal toxicity was more frequent in patients with a greater weight loss.…”

Section: Discussioncontrasting

confidence: 57%

“…BrieXy, oxaliplatin was administered as a 2-h infusion on days 1,8,15,29,37,43,50, 57 at a dose of 60 mg/m 2 , as previously established in our single-center phase I study, on rectal cancer [4], and was followed by leucovorin 20 mg/m 2 over 10Ј and a continuous infusion of Xuorouracil 200 mg/ m 2 per day over days 1-22 and 29-64. Patients received the planned treatment with no dose reduction if they had a neutrophil count¸1,500 l ¡1 and a platelet count¸100,000 l ¡1 ; otherwise chemotherapy was delayed until complete toxicity recovery. Treatment modiWcations were speciWed for hematological, gastrointestinal and neurological toxicity using the NCI Common Toxicity Criteria version 2.0.…”

Section: Chemotherapymentioning

confidence: 99%

“…In advanced (T3 and T4) esophageal cancer, a complete clearance of tumor cells is more diYcult to obtain [34]. A weekly schedule, which should optimize the inhibition of sub-lethal radiation-induced DNA damage repair [4,11], might increase the pathological complete response (pCR) rate through greater tumor shrinkage. In a phase I study, our group demonstrated that oxaliplatin, given weekly in combination with full-dose infusional FU and RT, is an active regimen in advanced rectal cancer [4].…”

Section: Introductionmentioning

confidence: 99%

“…A weekly schedule, which should optimize the inhibition of sub-lethal radiation-induced DNA damage repair [4,11], might increase the pathological complete response (pCR) rate through greater tumor shrinkage. In a phase I study, our group demonstrated that oxaliplatin, given weekly in combination with full-dose infusional FU and RT, is an active regimen in advanced rectal cancer [4]. The favorable toxicity proWle of this regimen, reXected in the high treatment compliance, the full dose of radiation delivered and the low surgical morbidity, prompted us to test this combination in locally advanced esophageal cancer (LAEC) patients.…”

Section: Introductionmentioning

confidence: 99%

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Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Chiarion-Sileni

Innocente

Cavina³

et al. 2008

Cancer Chemother Pharmacol

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Purpose The aim of this study was to evaluate the activity and safety of oxaliplatin/5-Xuorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer. Methods Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m 2 ), and leucovorin (20 mg/m 2 on days 1, 8,15,29,36,43,50,57) followed by continuous infusion Xuorouracil (200 mg/m 2 per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemoradiotherapy completion. The primary endpoint was 1-year progression-free survival. Results Forty (68%) patients completed treatment without modiWcations. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR.At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent. Conclusions Concurrent oxaliplatin, leucovorin, Xuorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.

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Section: Discussioncontrasting

confidence: 57%

Section: Chemotherapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Chiarion-Sileni

Innocente

Cavina³

et al. 2008

Cancer Chemother Pharmacol

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“…Using the pCRT approach, the rate of local recurrence at 5-year ranges from 6 to 8%, 1,2 and the rate of complete pathological response ranges from 4 to 44% of cases, as reported in single institution series trials, 3,4 in phase II studies [5][6][7] and in randomized trials. 2,8 For patients with good pathologic response to pCRT, the oncological outcome has been reported to be better for 'responders' than for 'nonresponders'.…”

Section: Introductionmentioning

confidence: 94%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C4G, which can affect radiosensitivity and MTHFR-677C4T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRGp2 (OR ¼ 0.46 95% CI 0.23-0.90, P ¼ 0.024; and OR ¼ 0.48 95% CI 0.24-0.96, P ¼ 0.034; respectively). An association trend was observed for ABCB1-3435C4T, which is responsible for the multi-drug resistance (odds ratio (OR) ¼ 1.96, 95% confidence interval (CI) 0.98-3.95, P ¼ 0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C4G as the most predictive factor. Other significant variables were: ABCB1-3435C4T, MTHFR-677C4T, ERCC1-8092C4A, ABCC2-1249G4A, XRCC1-28152G4A, XRCC3-4541A4G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRGp2 as compared with low profiles (OR ¼ 4.12 95% CI 1. Po0.001 and OR ¼ 12.44, Po0.0001, respectively). This study evidences a major role of hOGG1-1245C4G and MTHFR-677C4T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response.

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Combination chemotherapy versus single agent chemotherapy during preoperative chemoradiation for resectable rectal cancer

Resende

Lustosa²,

Menandro

et al. 2010

Cochrane Database of Systematic Reviews

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A phase I–II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer

Abstract: Weekly OXA, at doses potentially active systemically, can be combined with full-dose, infused FUra and radiotherapy. Given the low toxicity and promising activity, this regimen is being compared to standard FUra-based pelvic chemoradiation in a randomised study.

Cited by 133 publications

References 33 publications

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

Combination chemotherapy versus single agent chemotherapy during preoperative chemoradiation for resectable rectal cancer

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