Treatment of Rhabdoid Tumor of the Kidney

In the Children's Oncology Group AREN0321 (NCT00335556) study, patients with rhabdoid tumor of the kidney or malignant rhabdoid tumor were treated with regimen UH1 or dose-reduced revised UH1, which included alternating three-drug combinations (vincristine/doxorubicin/cyclophosphamide and carboplatin/cyclophosphamide/etoposide). Revised UH1 was used to decrease the toxicity from UH1. This trial included a window therapy study to evaluate the efficacy of vincristine/irinotecan. Results from this trial were compared with those from the NWTS-5 trial (regimen included carboplatin/etoposide alternating with cyclophosphamide [regimen RTK]).[25]

In the Children's Oncology Group AREN0321 (NCT00335556) study, patients with rhabdoid tumor of the kidney or malignant rhabdoid tumor were treated with regimen UH1 or dose-reduced revised UH1, which included alternating three-drug combinations (vincristine/doxorubicin/cyclophosphamide and carboplatin/cyclophosphamide/etoposide). Revised UH1 was used to decrease the toxicity from UH1. This trial included a window therapy study to evaluate the efficacy of vincristine/irinotecan. Results from this trial were compared with those from the NWTS-5 trial (regimen included carboplatin/etoposide alternating with cyclophosphamide [regimen RTK]).[25]

Patients treated in the AREN0321 study had significantly improved EFS and OS, compared with those treated in the NWTS-5 trial (4-year EFS rate, 23.1% vs. 16.7%; P = .020; 4-year OS rate, 30.6% vs. 20.0%; P = .014).

In the Children's Oncology Group AREN0321 (NCT00335556) study, patients with rhabdoid tumor of the kidney or malignant rhabdoid tumor were treated with regimen UH1 or dose-reduced revised UH1, which included alternating three-drug combinations (vincristine/doxorubicin/cyclophosphamide and carboplatin/cyclophosphamide/etoposide). Revised UH1 was used to decrease the toxicity from UH1. This trial included a window therapy study to evaluate the efficacy of vincristine/irinotecan. Results from this trial were compared with those from the NWTS-5 trial (regimen included carboplatin/etoposide alternating with cyclophosphamide [regimen RTK]).[25]

Improvement in outcome was mostly driven by patients with stage I/II disease. Patients with stage I/II disease treated in AREN0321 had an improved 4-year EFS rate, compared with patients treated in NWTS-5 (83.3% vs. 50.0%; HR, 0.24). Similarly, for these patients, the OS rate was 100% in AREN0321, compared with 50.0% in NWTS-5 (P = .03). Among patients with stage III/IV disease, there was no difference in EFS or OS between the two studies. Patients with stage III/IV disease achieved long-term EFS rates of 12% to 13% (HR, 0.80) and 4-year OS rates of 17% to 18% in both cohorts (HR, 0.80).

In the Children's Oncology Group AREN0321 (NCT00335556) study, patients with rhabdoid tumor of the kidney or malignant rhabdoid tumor were treated with regimen UH1 or dose-reduced revised UH1, which included alternating three-drug combinations (vincristine/doxorubicin/cyclophosphamide and carboplatin/cyclophosphamide/etoposide). Revised UH1 was used to decrease the toxicity from UH1. This trial included a window therapy study to evaluate the efficacy of vincristine/irinotecan. Results from this trial were compared with those from the NWTS-5 trial (regimen included carboplatin/etoposide alternating with cyclophosphamide [regimen RTK]).[25]

In AREN0321, all three patients who received the window therapy had progressive disease, leading to closure of the window therapy study for rhabdoid tumor of the kidney and malignant rhabdoid tumor.

In the Children's Oncology Group AREN0321 (NCT00335556) study, patients with rhabdoid tumor of the kidney or malignant rhabdoid tumor were treated with regimen UH1 or dose-reduced revised UH1, which included alternating three-drug combinations (vincristine/doxorubicin/cyclophosphamide and carboplatin/cyclophosphamide/etoposide). Revised UH1 was used to decrease the toxicity from UH1. This trial included a window therapy study to evaluate the efficacy of vincristine/irinotecan. Results from this trial were compared with those from the NWTS-5 trial (regimen included carboplatin/etoposide alternating with cyclophosphamide [regimen RTK]).[25]

When studies were pooled, there was no difference in outcomes based on tumor location (renal vs. extrarenal primary disease).

The NWTS-5 trial closed the arm for patients with rhabdoid tumor who were treated with cyclophosphamide, etoposide, and carboplatin because poor outcomes were observed. Combinations of etoposide and cisplatin; etoposide and ifosfamide; and ifosfamide, carboplatin, and etoposide (ICE chemotherapy) have been used.[26,27]

No formal trial has yet shown an advantage of higher-dose alkylator therapy (e.g., cyclophosphamide doses of 4.2 g/m2/cycle) or high-dose chemotherapy with stem cell rescue for non-CNS rhabdoid tumors.[28] A retrospective analysis from the Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) group found no benefit using high-dose chemotherapy with stem cell rescue for patients with rhabdoid tumor of the kidney.[29]

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

For the entire group, the 2-year event-free survival (EFS) rate was 37%, and the OS rate was 38%.

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

Patients with multifocal involvement (n = 12) had significantly inferior survival than did patients with pulmonary or mediastinal metastases or local disease.

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

Patients who underwent up-front chemotherapy had a lower, but not statistically significant, 2-year EFS rate than did patients who underwent immediate surgical resection.

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

Younger age (<12 months) and local stage III disease were associated with significantly inferior survival than were stage I and stage II disease.

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

No difference was seen in 2-year EFS rates for patients without progression within 90 days consolidated by high-dose hematopoietic stem cell transplant (HSCT) (n = 10) compared with patients without consolidation by HSCT (n = 21).

A retrospective analysis of 58 patients with malignant rhabdoid tumor of the kidney from the International Society of Paediatric Oncology (SIOP), GPOH, and European Rhabdoid Tumor Registry was performed.[29]

In a separate analysis of the same patient population, investigators examined the role of radiation therapy for local control in patients with higher-stage disease. Twenty-one patients (stages II and III) received radiation therapy during first-line treatment, 18 of whom received radiation therapy to all involved sites. The local failure rate was 29% for patients with local stage II or stage III disease who received radiation therapy to all sites, compared with 68% for nonirradiated patients. The progression-free survival rate was 67% for patients with local stage II and stage III disease who were treated with radiation therapy during first-line treatment (adjusted for early relapse or treatment abandonment), compared with 15% for patients who did not receive radiation therapy (P < .0001).[30][Level of evidence C1]