Radioembolization of Liver Metastases From Colorectal Cancer Using Yttrium-90 Microspheres With Concomitant Systemic Oxaliplatin, Fluorouracil, and Leucovorin Chemotherapy

Sharma, Ricky A.; Hazel, Guy A. Van; Morgan, Bruno; Berry, David P.; Blanshard, K.; Price, D. A.; Bower, G; Shannon, Jennifer; Gibbs, Peter; Steward, William P.

doi:10.1200/jco.2006.08.7916

Cited by 287 publications

(195 citation statements)

References 32 publications

(9 reference statements)

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“…These rates compare favorably with other reported cohorts who received Y90 treatment. [19][20][21] Significant adverse events to Y90 therapy usually are GI in nature. This is most likely because of the inadvertent deposition of microspheres into the GI tract through unrecognized collateral vessels, leading to ulcer formation.…”

Section: Discussionmentioning

confidence: 99%

Radioembolization of colorectal hepatic metastases using yttrium‐90 microspheres

Mulcahy

Lewandowski

Ibrahim

et al. 2009

Cancer

156

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BACKGROUND:The objective of the current study was to determine the safety and efficacy of Yttrium‐90 (Y90) microsphere treatment in patients with liver‐dominant colorectal metastases.METHODS:Seventy‐two patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 120 Gray (Gy). Safety and toxicity were assessed using version 3 of the National Cancer Institute Common Terminology Criteria. Response was assessed by anatomic imaging and positron emission tomography (PET). Survival from the diagnosis of hepatic metastases and first treatment were estimated using the Kaplan‐Meier method. Substratification analyses were performed.RESULTS:The median dose delivered was 118 Gy. Treatment‐related toxicities included fatigue (61%), nausea (21%), and abdominal pain (25%). Grade 3 and 4 bilirubin toxicities were observed in 9 of 72 patients (12.6%). The tumor response rate was 40.3%. The median time to hepatic progression was 15.4 months, and the median response duration was 15 months. The PET response rate was 77%. Overall survival from the first Y90 treatment was 14.5 months. Tumor replacement (≤25% vs >25%) was associated with significantly greater median survival (18.7 months vs 5.2 months). The presence of extrahepatic disease was associated negatively with overall survival (7.9 months vs 21 months). Overall survival from the date of initial hepatic metastases was 34.6 months. A subset analysis of patients who had an Eastern Cooperative Oncology Group performance status of 0 demonstrated a median survival of 42.8 months and 23.5 months from the time of hepatic metastases and Y90 treatment, respectively.CONCLUSIONS:Y90 liver therapy appears to provide sustained disease stabilization with acceptable toxicity. Asymptomatic patients with preserved liver function at the time of Y90 appeared to benefit most from treatment. Cancer 2009. © 2009 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Radioembolization of colorectal hepatic metastases using yttrium‐90 microspheres

Mulcahy

Lewandowski

Ibrahim

et al. 2009

Cancer

156

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“…Basierend auf den Daten einer Phase-I-Studie wurde die Kombination von SIRT mit einer FOLFOX-Chemotherapie in 3 randomisierten Multicenterstudien (SIRFLOX, FOXFIRE und FOXFIRE global) untersucht [1205].…”

Section: Hintergrundunclassified

S3-Leitlinie – Kolorektales Karzinom

Schmiegel

Buchberger

Follmann³

et al. 2017

Z Gastroenterol

136

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“…A number of large scale studies using FOLFOX or its variants have consistently yielded RECIST response rates of 50-60%, progression-free survival of 8-9 months and median survival of 16-18 months [25]. Sharma et al [26] reported promising results from a Phase I-II trial of FOLFOX chemotherapy in combination with RE for patients with unresectable colorectal liver metastases in the first line setting. Twenty patients were treated with oxaliplatin at escalating doses of 30-85mg/m 2 and full dose 5LV/5FU for Cycle 1-3 and full dose FOLFOX 4 for cycles 4-12.…”

Section: Optimal Combinations Of Systemic Chemotherapy With Re In Metmentioning

confidence: 99%

“…The practice at our institution is to offer oxaliplatin and 5-FU chemotherapy (in the dosing regime shown to be safe in reference [26]) with RE as second line or subsequent line therapy for patients with liver-dominant or liver-only metastases from colorectal cancer, regardless of their previous chemotherapy history. In patients who have experienced unacceptable toxicity with oxaliplatin (e.g.…”

Section: Guidelines For Combining Re With Systemic Chemotherapymentioning

confidence: 99%

“…It should be noted that, since the biological mechanism of radiosensitisation (as discussed above) may be independent of the mechanism of anti-cancer efficacy of the same drugs used without concomitant radiotherapy, there is a scientific rationale for using a radiosensitising chemotherapy drug that the patient has previously received and may even have previously shown "tumor resistance" to. Oxaliplatin, 5-FU and irinotecan are all radiosensitisers, and the selection of radiosensitising chemotherapy in clinical practice should be guided by the dosing regimes shown to be safe with RE [26,27,32] rather than by the need to control microscopic or macroscopic disease outside the liver. Following the administration of radiosensitising chemotherapy with RE, the patient can subsequently receive a systemic regime which may offer further survival benefit.…”

Section: Guidelines For Combining Re With Systemic Chemotherapymentioning

confidence: 99%

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Multi-modality Therapy of Hepatic Metastases from Colorectal Carcinoma: Optimal Combination of Systemic Chemotherapy with Radio-embolization

Hill¹,

Sharma²

2011

J Nucl Med Radiat Ther

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Despite major advances in the systemic treatment of metastatic colorectal carcinoma, the 5 year survival rate remains disappointingly low at approximately 7% [1]. Median survival for this patient group is currently in the range 1.5 to 2.5 years, and depends on continuation of systemic therapy for much of the patient's remaining life. Of all patients with metastatic colorectal cancer, 20-30% have liver-only metastases and approximately 50% of recurrences following resection of the primary tumour are confined to the liver alone. Surgical resection of hepatic metastases is the treatment of choice, where possible, but this is feasible for less than 15% of patients at presentation [2]. For the subset of patients with metastatic colorectal cancer in whom surgical resection can be achieved, the 5 year overall survival probability is 30-40%, with 20% of patients achieving long-term cure [3]. Patients with unresectable liver predominant metastases have increasingly become a focus of interest for improving survival for patients with metastatic colorectal cancer. This prioritization is due to the outcomes from Phase II studies utilising downstaging neo-adjuvant chemotherapy in which 10-20% of patients with inoperable liver disease have been converted to curative resection and due to the finding that there is a statistical correlation between tumour response and resection rates across clinical studies [4]. Multimodality treatment combinations of systemic agents with liver surgery have been proffered as a means of improving tumour response rates and so improving the proportion of long term survivors of patients with metastatic colorectal cancer.There has been much optimism that newly developed, expensive, biologically targeted agents may improve survival in this patient group, when combined with systemic chemotherapy, but complete radiological responses or cures remain exceedingly rare. Preliminary data from Phase III trials of chemotherapy and biologically targeted agents have not consistently shown statistically significant increases in response rates,nor the frequency of down-staging to resectability, over chemotherapy alone. There are two limitations of delivering neoadjuvant chemotherapy prior to liver metastectomy. Firstly, the development of pathological liver steatosis and fibrosis, which can occur with oxaliplatin-based chemotherapy or with irinotecan-based chemotherapy, and worsens with cumulative dosing. Secondly, the risk of disease relapse in the liver post-surgery, usually not at the resection site. Of those patients with liver-dominant or liver-only metastases, where the hepatic disease is unlikely to become resectable even with neoadjuvant systemic therapy, there is still a robust rationale for maximising local control of the liver disease, since up to 90% of patients with metastatic colorectal cancer ultimately die of liver failure [5]. Multiple loco-regional strategies are therefore under investigation to improve the outcome for patients with unresectable colorectal liver metastases, including radio-frequen...

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Radioembolization of Liver Metastases From Colorectal Cancer Using Yttrium-90 Microspheres With Concomitant Systemic Oxaliplatin, Fluorouracil, and Leucovorin Chemotherapy

Abstract: The maximum-tolerated dose was 60 mg/m2 of oxaliplatin for the first three cycles, with full FOLFOX4 doses thereafter. This chemoradiation regime merits evaluation in phase II-III trials.

Cited by 287 publications

References 32 publications

Radioembolization of colorectal hepatic metastases using yttrium‐90 microspheres

Radioembolization of colorectal hepatic metastases using yttrium‐90 microspheres

S3-Leitlinie – Kolorektales Karzinom

Multi-modality Therapy of Hepatic Metastases from Colorectal Carcinoma: Optimal Combination of Systemic Chemotherapy with Radio-embolization

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