Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

Ilson, David H.; Bains, Manjit S.; Kelsen, David P.; O'Reilly, Eileen Mary; Karpeh, Martin S.; Coit, Daniel G.; Rusch, Valerie W.; Gönen, Mithat; Wilson, Katie; Minsky, Bruce D.

doi:10.1200/jco.2003.02.147

Cited by 90 publications

(54 citation statements)

References 25 publications

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“…This result, together with that of others, seems to imply that surgical resection could be useful at least in some patients (Adelstein et al, 2000;Ilson et al, 2003). No conclusions can be drawn on the utility of HDR-EBT in the local control of disease from our data, as few patients received this treatment.…”

Section: Discussioncontrasting

confidence: 62%

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Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Chiarion-Sileni

Corti

Ruol³

et al. 2007

Br J Cancer

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This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m À2 , cisplatin 75 mg m À2 on day 1 and fluorouracil 750 mg m À2 day À1 on days 2 -5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m À2 week À1 for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week À1 ). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2 -66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1 -12.4), and the 1-and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3 -4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified.

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Section: Discussioncontrasting

confidence: 62%

“…A change in the chemotherapy schedule, like the use of weekly doses, might help to reduce the acute tumour necrosis and permit wall repair (Ilson et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Chiarion-Sileni

Corti

Ruol³

et al. 2007

Br J Cancer

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“…Recent studies have from our institution have also indicated that using non-5-FU containing chemotherapy regimens with concurrent radiotherapy may also have a potential to lower toxicity of combined chemoradiotherapy. In two phase I trials combining either weekly paclitaxel (Brenner et al, 2004) or weekly irinotecan (Ilson et al, 2003) with a weekly schedule of relative low-dose cisplatin and concurrent radiotherapy, gastrointestinal, and haematologic toxicities were relatively mild. These regimens also offer promise as an alternative to conventional 5-FU and cisplatin.…”

Section: Discussionmentioning

confidence: 99%

Combined modality chemoradiation in elderly oesophageal cancer patients

et al. 2007

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We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66 -88) with a diagnosis of stage II -III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3 -4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months and 2-year survival 64%. There was no significant difference in overall survival between Charlson score p2 and those with a score X2 (P ¼ 0.10). Similar survival was observed for patients with adenocarcinoma or squamous carcinoma. Primary chemoradiation with two cycles of 5-FU, mitomycin-C, and 50.4 Gy in elderly patients is an active regimen with moderate toxicity, despite the advanced age and heavy comorbidity burden of this cohort. Patients with local/regional oesophageal cancer with adequate functional status should not be excluded from potentially curative treatment based on age alone.

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“…The present study is to our knowledge the first phase II trial evaluating in a population of inoperable patients with the regimen defined in phase I (Ilson et al, 2003). The main results of the present study were the complete clinical response rate of 58.1% (95% CI, 43.4 -72.8%), overall survival rate of 27.9% (95% CI: 13.4 -41.3%) at 2 years and the absence of significant improvement of dysphagia after induction chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Phase I -II studies of weekly irinotecan and radiation therapy have been performed (Koukourakis et al, 1999;Takeda et al, 1999). Recently, phase I study of weekly with cisplatin -irinotecan chemotherapy followed by chemo-radiotherapy in locally advanced oesophageal cancer has been reported (Ilson et al, 2003). The dose-limiting toxicity was primarily myelosuppression, no grade 3 or 4 oesophagitis, diarrhoea or stomatitis was observed.…”

mentioning

confidence: 99%

Induction cisplatin–irinotecan followed by concurrent cisplatin–irinotecan and radiotherapy without surgery in oesophageal cancer: multicenter phase II FFCD trial

et al. 2006

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A recent phase I study showed that weekly cisplatin, irinotecan and concurrent radiotherapy can be administered with moderate toxicity in patients with oesophageal cancer. Patients with no prior treatment and oesophageal cancer stage I to III, performance status o3, caloric intake 41500 kcal day À1 were included. Chemotherapy, with cisplatin 30 mg m À2 and irinotecan 60 mg m À2 , was administered at days 1, 8, 22, 29, and concurrently with radiotherapy at days 43, 50, 64 and 71. Radiotherapy was delivered with 50 or 50.4 Gy in 25 fractions/5 weeks. Forty-three patients were included, 10 stage I, 19 stage II and 14 stage III. Mean age was 59.2 years (range 44 -79). A total of 30 out of 43 (69.8%) patients underwent all planned treatment. During induction chemotherapy, 14 severe toxicities of grade 3 or 4 in 10 patients (23.3%) were reported with 57.1% due to haematoxicity. During chemoradiotherapy, 31 severe toxicities of grade 3 or 4 with 64.5% due to haematotoxicity were reported in 18 patients. One toxic death occurred (diarrhoea grade 4). The complete clinical response rate was 58.1% (95% CI: 43.4 -72.8%). Overall survival rate at 1 and 2 years was 62.8%, (95% CI, 58.3 -77.3%) and 27.9% (95% CI, 13.4 -41.3%), respectively. In conclusion, cisplatin -irinotecan -radiotherapy is an active and well-tolerated regimen feasible in out-patients.

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Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

Cited by 90 publications

References 25 publications

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

Combined modality chemoradiation in elderly oesophageal cancer patients

Induction cisplatin–irinotecan followed by concurrent cisplatin–irinotecan and radiotherapy without surgery in oesophageal cancer: multicenter phase II FFCD trial

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