Treatment of Fluorouracil-Refractory Patients With Liver Metastases From Colorectal Cancer by Using Yttrium-90 Resin Microspheres Plus Concomitant Systemic Irinotecan Chemotherapy

Hazel, Guy A. Van; Pavlakis, Nick; Goldstein, David; Olver, Ian; Tapner, Michael; Price, D. A.; Bower, G; Briggs, Gregory M.; Rossleigh, Monica A.; Taylor, Denise; George, Jacob

doi:10.1200/jco.2008.20.8116

Cited by 145 publications

(74 citation statements)

References 34 publications

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“…In an important study of a radiosensitising drug other than oxaliplatin, Van Hazel et al [27] perfomed a Phase I dose escalation study using single agent Irinotecan and RE in twenty-five patients with liver only or liver-dominant colorectal metastases who were refractory to 5-FU but had never received Irinotecan previously. Patients were treated with Irinotecan at escalating doses between 50 and 100 mg/ m 2 Days 1 and 8 of a 21 day cycle for 2 cycles, with RE administered during cycle 1 and subsequently received full dose Irinotecan at 100 mg/m 2 Days 1 and 8 for cycles 3 to 9.…”

Section: Clinical Rationale For Combining Re With Chemotherapy For Sementioning

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%

“…In patients who have experienced unacceptable toxicity with oxaliplatin (e.g. persistent peripheral neuropathy), RE can be combined with infusional 5FU [32] or with irinotecan [27], using the dosing regimes of chemotherapy shown to be safe. Our current practice is to administer RE on day 2, 3 or 4 of cycle 1 and to administer 6 weeks of chemotherapy in total for radiosensitisation.…”

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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Section: Clinical Rationale For Combining Re With Chemotherapy For Sementioning

confidence: 99%

Section: Guidelines For Combining Re With Systemic Chemotherapymentioning

confidence: 99%

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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“…Selective internal radiation therapy (SIRT) with yttrium-90 ( 90 Y)-emitting microspheres is increasingly recognized as an effective therapy of both primary and secondary hepatic malignancies [1][2][3][4][5]. Increasing reports have shown this to be a useful treatment for unresectable hepatic metastases from colorectal carcinoma [6], neuroendocrine tumors [7], and primary hepatocellular carcinoma [3,8,9].…”

Section: Case Reportmentioning

confidence: 99%

“…Recent reports have described their use as monotherapy for inop- erable hepatoma [3,5], as well as in combination with chemotherapy for unresectable hepatic metastases from colorectal cancer [1]. Although potentially an effective therapy, a number of complications can occur, even in the hands of an experienced operator.…”

Section: Sir-spheres Consist Of Microspheres Containingmentioning

confidence: 99%

A Serious Complication of Selected Internal Radiation Therapy: Case Report and Literature Review

2010

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The use of selective internal radiation therapy (SIRT) with SIR-Spheres (Sirtex, Sydney, Australia) is increasingly recognized as a potential therapeutic modality of primary and secondary malignant liver tumors. A number of treatment-related complications have been described despite technical expertise and detailed pretreatment investigations to assess suitability. We describe a case of gastric ulceration from nontargeted deposition of SIR-spheres in the gastric mucosa with life-threatening consequences. This case highlights the need for careful screening and appropriate patient selection, and the need to recognize ulceration from SIRT as a potential complication of treatment. The characteristic endoscopic, radiologic, and histopathologic findings are illustrated and recommendations are reviewed with regard to the current literature. The Oncologist 2010;15:830 -835 CASE REPORTSelective internal radiation therapy (SIRT) with yttrium-90 ( 90 Y)-emitting microspheres is increasingly recognized as an effective therapy of both primary and secondary hepatic malignancies [1][2][3][4][5]. Increasing reports have shown this to be a useful treatment for unresectable hepatic metastases from colorectal carcinoma [6], neuroendocrine tumors [7], and primary hepatocellular carcinoma [3,8,9]. A number of treatment-related complications have been described despite technical expertise and detailed pretreatment investigations to assess suitability. We describe a case of gastric ulceration from aberrant deposition of SIR-Spheres (Sirtex, Sydney, Australia) in the gastric mucosa with lifethreatening consequences.The patient, a 63-year-old male with metastatic colorectal cancer, received SIRT 17 weeks earlier at another institution for recurrent, inoperable hepatic metastatic disease. The original diagnosis of rectosigmoid adenocarinoma was made 3 years earlier following an episode of infective endocarditis with Streptococcus viridians.

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Prognostic factors and prevention of radioembolization-induced liver disease

Gil-Alzugaray¹,

Chopitea²,

et al. 2013

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Radioembolization (RE)‐induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low‐dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P < 0.0001). Treatment efficacy was not jeopardized since 3‐month disease control rates were virtually identical in both groups (66.7% and 67.2%, P = 0.93). Exposure to chemotherapy in the 2‐month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2013)

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Treatment of Fluorouracil-Refractory Patients With Liver Metastases From Colorectal Cancer by Using Yttrium-90 Resin Microspheres Plus Concomitant Systemic Irinotecan Chemotherapy

Abstract: Concomitant use of radioembolization plus irinotecan did not reach a maximum-tolerated dose. The recommended dose of irinotecan in this setting is 100 mg/m(2) on days 1 and 8 of a 3-week cycle.

Cited by 145 publications

References 34 publications

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

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

A Serious Complication of Selected Internal Radiation Therapy: Case Report and Literature Review

Prognostic factors and prevention of radioembolization-induced liver disease

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