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Literature citation: boeken, t., moussa, n., pernot, s., abed, a., dean, c., taieb, j., sapoval, m., & pellerin, o.(2020).Does bead size affect patient outcome in irinotecan-loaded beads chemoembolization plus systemic chemotherapy regimens for liver-dominant colorectal cancer? results of an observational study.Cardiovascular and interventional radiology, 43(6), 866-874.Https://doi.Org/10.1007/s00270-020-02438-0.Manufacturer comments: dc bead was reported to have been used in the treatment of these patients.The equivalent product lc bead is available in the usa and is indicated for the treatment of hypervascular tumors and avms.The reported events were identified as part of a literature review.Patients received treatment with dc bead loaded with irinotecan between march 2009 and january 2018.The author reported: immediate and delayed adverse events associated with debiri of 25 patients 70-150 um beads: pancreatitis 5 (5%), cholecystitis 2 (2%); biloma 2 (2%); hypothermia 6 (6%); stroke 1 (1%); aortic dissection 1 (1%); pulmonary edema 3 (3%).100 - 300 um beads: pancreatitis 1 (2%); biloma 2 (3%); hypothermia 1 (2%); pulmonary edema 1 (2%).The author claims there is a new set of post-embolization symptoms consisting of hypothermia and hypertension that was severe in nature.This is not the normal sequence of aes we see with pes.While the events of aortic dissection, stroke and pulmonary edema are a sequale of hypertension, the author believes that the hypertension was attributed to the device.This study is from a single site with a small number of patients experiencing what they are calling pes so we cannot draw any conclusions since it could be attributed to other standard practices at the facility.It is indicated that the device will not be returned for evaluation; therefore a failure analysis of the complaint device could not be completed.No batch review was possible for this case as the batch number has not been provided.No product malfunction/deficiency has been identified.No corrective/preventative action has been identified.Based on a thorough review of the reported complaint, the most probable cause for this complaint was considered known inherent risk of device.The reported adverse events are known and documented in the labeling (including both short or long term known complications or adverse reactions).Based on the results of this investigation, no escalation is necessary.Should we receive any information to enable further investigations, a follow-up report will be submitted.At this time this report is considered final.
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Review of literature article, does bead size affect patient outcome in irinotecan loaded beads chemoembolization plus system chemotherapy regimens for liver dominant colorectal cancer.Results of an observational study.Author tom boeken et al.Abstract: purpose: we investigated the clinical effects of bead size in irinotecan loaded beads chemoembolization (debiri) used for treating liver dominant colorectal cancer.Materials and methods: between march 2009 and january 2018, all consecutive patients with colorectal cancer liver metastases referred for debiri at our tertiary centre were included in an observational study.Patients were treated exclusively with either 100 mg irinotecan loaded dc beads of 70 to 150 um (small bead group or sb) or 100 to 300 um (large bead group or lb) in diameter, in addition to systemic therapy.Liver tumour response rate at 3 months, liver and overall progression free survival (pfs) and overall survival were estimated.Results: in total, 84 patients with liver dominant progressive disease underwent 232 debiri sessions.Fifty four patients were treated in the sb group and 30 patients in the lb group.Liver progression free rates at 3 months were 86.7% for the lb group and 79.6% for the sb group (ns).Median liver pfs and overall pfs were, respectively, 7.15 months and 7.15 months for the lb group and 7.65 and 7.55 months for the sb group (ns).Median overall survival was 13.04 months for the lb group and 15.59 months for the sb group (p equals 0.04).Specific treatment grade 3 + 4 toxicity occurrence was 5 (17%) in the lb group and 20 (37%) in the sb group.Conclusion: no significant difference in patient outcome was observed between debiri bead sizes of 70 to 150 um and 100 to 300 um.A trend toward higher treatment specific toxicity was observed with the smaller beads.Results: patients and procedures: from march 2009 to january 2018, 84 consecutive patients with progressive colorectal liver-dominant disease were included in this debiri cohort.The intention to treat population included all 84 patients.Seventy one patients had a liver-restricted disease and lung metastases in 11 patients and one patient, respectively, for the sb group and the lb group.One patient had limited peritoneal carcino matosis in the sb group.Patients had previously undergone a median of 3 (range 2 to 6) lines of systemic treatment in both groups, and all had received both irinotecan and oxaliplatin.The ecog ps was 0 in 53 patients (63%), 1 in 26 patients (31%) and 2 in 5 patients (6%).The liver was burden 25% in 26 patients (31%), from 26% to 50% and in 34 patients (40%) 50% in 24 patients (29%).All patients had progressive disease at baseline.The tumours were wild type for kras/braf in 43% and 50% of the patients, respectively, in the sb group and the lb group.In total, 232 debiri sessions were performed, 38 patients were scheduled for two sessions, and 46 patients were scheduled for four sessions.The two session plan consisted in the treatment with 200 mg of irinotecan of lobe 1 and then lobe 2, respectively, on day 0 and day 30.The four session plan consisted in the treatment with 100 mg of irinotecan of lobe 1 and then lobe 2 alternatively on day 0, day 15, day 30 and day 45.Sixty six (79%) patients received systemic chemotherapy, as follows.Capecitabine was given to 43 (51%) patients, folfox and bevacizumab to 18 (21%) patients and regorafenib to 5 (6%) patients.Regorafenib and capecitabine were not suspended.Bevacizumab was suspended two weeks prior to each session.If systemic therapy was due on the same day as the debiri session, exclusive intravenous 5 fu was administered.Full debiri treatment, define as the successful injection of 200 mg irinotecan into each lobe, was recorded for 74% (n equals 40) of patients in the sb group and for 87% (n equals 26) of patients in the lb group.The remaining (n equals 18) patients did not receive full treatment due to the cancelation of debiri procedures: clinical condition was too poor in seven patients, four patients were diagnosed with interval progressive disease, six patients had post-procedure pancreatitis, and one patient had post procedure cholecystitis.These specific complications are detailed in the tolerance section.Fifty four patients were treated with 70 to150 um beads (small beads or sb) between march 2009 and february 2016, and 30 patients received 100 to 300 um dc beads (large beads or lb) between march 2016 and january 2018.All beads were loaded with 100 mg of irinotecan per vial.Adverse events: expected toxicities, according to the ctcae grading system, did not differ between the two groups, with a median of 1 grade 3 treatment-related event per patient.However, two specific toxicities requiring further consideration were identified.The usual post embolization syndrome which is a well known side effect of chemoembolization associates with pain, hyperthermia, an inflammatory biological syndrome and hepatic cytolysis.Interestingly, all the patients in this cohort experienced a different post embolization syndrome with pain, hypothermia high blood pressure.All had normal map before the procedure, including those with preexisting hypertension or on vegf antagonist treatment.Hypertension of grade 3 or above has not been reported with doxorubicin beads or lipiodol chemo embolization, and irinotecan is mostly known to have cholinergic effects, such as bradycardia.However, hypertension was reported following the injection of free irinotecan/supernatant in one study.The hypertension induced by debiri may be a consequence of the severe pain reported by patients during the procedure (median intraprocedural vas score was 8 in our series), and the pain was concomitant with the increase in blood pressure.However, no concomitant tachycardia resembling that usually observed in pain related hypertension was detected here.Moreover, map remained high despite aggressive pharmacological pain control.This specific triad can be found in seven cases in the series of 330 patients published by martin et al.The mechanisms underlying this triad immediately following debiri embolization remain unknown.Proactive management of this specific post embolization syndrome should be encouraged.Embolization related specific complications, such as cholecystitis and pancreatitis in particular, were more frequent in the sb group than in the lb group, consistent with previous assumptions about nontarget embolization.Though pancreatitis is also a known and rare side effect of intravenous administration of irinotecan, its high occurrence in our study suggests a different mechanism.This could be explained by either the intra arterial drug administration or the technique with direct nontarget embolization.There is a trend toward more pancreatic and biliary complications in the sb group.The use of 70 to 150 lm beads might need greater attention when placing the microcatheter downstream to nontarget arteries and searching for any back flow or unusual anastomosis that will contribute to nontarget embolization.Our study has several limitations.This single centre cohort consisted of patients referred for debiri as a salvage therapy and consequently was highly heterogeneous, with a median of three previous lines of treatment, which is more than in other published series.This might explain why the os was several months shorter than that in the only phase iii debiri trial performed to date, in which debiri was evaluated as a first line therapy.The liver pfs of (7 months obtained here for patients with three or more previous lines of treatment is promising.However, we did not compare debiri with other standard treatments and were not able to perform a statistical analysis indicating the optimal place of this approach in cancer management.Reported immediate and delayed adverse events associated with debiri (25 patients) 70 to150 um beads: pancreatitis 5 (5%), cholecystitis 2 (2%); biloma 2 (2%); hypothermia 6 (6%); stroke 1 (1%); aortic dissection 1 (1%); pulmonary edema 3 (3%).100 to 300 um beads: pancreatitis 1 (2%); biloma 2 (3%); hypothermia 1 (2%); pulmonary edema 1 (2%).
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