Irinotecan may effectively treat Wilms tumor in some pediatric patients

Robyn Boyle, RPh, for MDLinx | June 06, 2018

Regimens containing irinotecan resulted in complete response (CR) or partial response (PR) in three of 14 patients with relapsed Wilms tumor (WT), according to a study published in Pediatric Blood & Cancer.


“Our results and the reviewed literature suggest some effectiveness of irinotecan in relapsed WT, especially combined with other agents,” wrote the authors.

Some prior studies showed that irinotecan, a camptothecin compound that interferes with DNA replication and cell division, has antitumor activity in relapsed Wilms tumor, but information is limited and randomized studies are not available.

The International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG), led by Janna A Hol, from the Princess Máxima Center for Pediatric Oncology in Utrecht, The Netherlands, set out to evaluate the response and outcome of irinotecan combined with other chemotherapeutic agents for metastatic diffuse anaplastic WT—a diagnosis with a poor prognosis.

Children 18 years of age or younger who had received irinotecan as part of a chemotherapeutic regimen for relapsed WT were identified for the study. High risk (HR) tumors included those with diffuse anaplasia or blastemal-type histology after preoperative chemotherapy. Intermediate risk (IR) tumors were either stromal, epithelial, focal anaplasia, mixed, or regressive histology.

Irinotecan response was defined as the best observed response after at least one cycle, derived from local reports and classified according to RECIST criteria as CR, PR, stable disease (SD), or progressive disease (PD). Toxicity was graded according to Common Terminology Criteria for Adverse Events.

A total of 16 patients were identified who had not been included in previous reports. The median age at relapse was five years, and the median time between first tumor diagnosis and relapse was ten months.

At diagnosis, most patients had advanced-stage disease (4 with stage I/II, 4 with stage III, 7 with stage IV), and one patient with bilateral disease.

Histology at diagnosis was classified as IR in seven patients and HR in nine patients, including four HR with diffuse anaplasia, and five HR with blastemal-type.

Response data were available for 14 patients. One showed CR (irinotecan combined with vincristine), two had PR, four had SD, and seven had PD. Overall, three of 14 (21%) patients were alive without disease at last follow-up, which ranged from 12 to 22 months.

The three patients with objective responses initially had IR histology (one CR and one PR) and HR blastemal-type histology (PR). Among the 11 patients who showed SD or PD, only one patient was alive without evidence of disease after 22 months. Among the four patients with initial HR-diffuse anaplasia, all died of disease within ten months.

Toxicity data were available for ten patients; hematological and gastrointestinal adverse events were the most commonly reported. There were no toxicity-related deaths.

In addition, the investigators searched the medical literature to find articles evaluating the administration of irinotecan in pediatric WT patients, including phase 1 and 2 trials, retrospective chart reviews, and case series. Four studies described CR or PR in eight relapsed patients treated with various dosages and regimens of irinotecan.

Objective responses were observed in cases where irinotecan was combined with vincristine and/or temozolomide (with and without bevacizumab), possibly due to a synergistic effect.

The researchers acknowledge that the study was limited by the retrospective design, as well as the heterogeneous treatment regimens of irinotecan.

“Our results and the reviewed literature suggest some effectiveness of irinotecan in relapsed WT, especially combined with other agents,” concluded the authors, who feel that prospective studies are needed.

To read more about this study, click here