Continuing response to subsequent treatment lines with tyrosine kinase inhibitors in an adolescent with metastatic renal cell carcinoma.

A 14-year-old girl with metastatic renal cell carcinoma was treated with nephrectomy, interferon, and several lines of the targeted agents sorafenib, bevacizumab, sunitinib, and everolimus, either alone or in combination. Treatment was well tolerated, but the patient developed hypothyroidism and significant hypertension with bevacizumab and sunitinib. She responded to all agents and was given radiation treatment twice at the time of symptomatic disease progression; she died 33 months from diagnosis.

Gefitinib in combination with oral topotecan and cyclophosphamide in relapsed neuroblastoma: pharmacological rationale and clinical response.

AIM: Activity and toxiciy of gefitinib in combination with topotecan and cyclophosphamide (CPA) were evaluated in a case-series of relapsed neuroblastoma (NB) patients. The in vitro activity of the combination was also assessed. PROCEDURE: Gefitinib (250 mg/day), topotecan (0.8 mg/m(2)/day), and CPA (50 mg/m(2)/day) (GTC) were administered orally for 14 consecutive days out of 28 days. Antitumor activity of gefitinib as single agent and in combination with either topotecan or CPA was assessed in a panel of NB cell lines. RESULTS: Ninety-two courses were given in 10 patients. Grade 4 neutropenia was observed in 7/92 courses (8%) and grade 4 thrombocytopenia in 8/92 (9%). Two patients had a grade 2 liver toxicity, four a grade 1/2 skin toxicity, and two a grade 1/2 diarrhea. Dose reduction of topotecan and/or CPA was required in eight patients. After four courses, three patients were in partial response (PR) and four with a stable disease (SD), while three experienced a progressive disease (PD). Time to progression (TTP) was 9 months (range, 1-27). After a median follow-up of 16 months (range 5-54), seven patients are died of disease (DOD) and three alive with disease (AWD). All but one patient discontinued oral chemotherapy because of a PD, whilst one patient stopped chemotherapy after 27 months with a SD. In vitro, gefitinib was synergistic with topotecan and additive with CPA. CONCLUSION: The GTC combination was well tolerated and the TTP was encouraging. These promising results, also supported by in vitro evidence, should be further confirmed in a phase II study.

Teratoma with a malignant somatic component in pediatric patients: the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.

BACKGROUND: Teratoma with a malignant somatic component (TMSC) is rare but described in adults, whereas information on pediatric presentation is sparse. PROCEDURE: The Associazione Italiana Ematologia Oncologia Pediatrica identified 14 cases of TMSC. Clinical files and pathology specimens were reviewed. RESULTS: The series (9 female, 5 male) showed the following disease: testis (2), sacrococcygeal (3), ovary (3), retroperitoneum (3), mediastinum (2), and foot soft tissue (1). Distribution of the somatic component was: carcinoma (4), pancreatic neuroendocrine tumor (1), neuroblastoma (3), rhabdomyosarcoma (3), rhabdomyosarcoma plus liposarcoma, chondrosarcoma, neurogenic sarcoma (1), chondrosarcoma plus neuroectodermal sarcoma (1), malignant peripheral nerve sheath tumor (1). Three patients were in stage I, four in stage II, three in stage III, and four in stage IV. All but one patient underwent surgery and only females showed carcinoma components. Nine patients relapsed or progressed and eight died. Six patients are alive and disease-free. Two patients underwent complete resection and four were treated based on transformed histologies. Relapse-free and overall survival rates were 35.7% and 42.8%, respectively (median follow-up, 31 months). CONCLUSIONS: Prognosis for germ cell tumors (GCTs) containing MSC is worse than that for GCTs. The pediatric disease appears to be more heterogeneous in tumor site distribution and MSC histology than in adults. Our series suggests no effects of age, histology, or gender on outcome. Surgery has an essential role in localized disease, with complete resection highly desirable. Chemotherapy optimized for histology should include reagents directed to the somatic malignancy, if chemosensitive. Malignant GCT warrants GCT-directed chemotherapy.

Successful treatment of trilateral retinoblastoma with conventional and high-dose chemotherapy plus radiotherapy: a case report.

Trilateral retinoblastoma (TRB) is a rare condition characterized by an intracranial neuroblastic tumor associated with bilateral or unilateral retinoblastoma (RB). The outcome is almost always fatal. An 18-month-old patient with familial bilateral RB was referred for a pineal lesion detected on a screening by magnetic resonance imaging. The child, considered inoperable by 2 different neurosurgical teams, was treated with conventional chemotherapy (methotrexate, vincristine, vepeside, cyclophosphamide, and carboplatin) plus tandem transplantation (vepeside/carboplatin and thiotepa/mephalan) followed by local radiotherapy. At 80 months from the diagnosis of TRB, the patient is alive and in complete remission, with no neuropsychologic consequences. An early and aggressive treatment may improve the prognosis of TRB.

A multimodal strategy based on surgery, radiotherapy, ICE regimen and high dose chemotherapy in atypical teratoid/rhabdoid tumours: a single institution experience.

PURPOSE: Atypical Teratoid/Rhabdoid Tumour is a rare and aggressive childhood tumour. The outcome of a series treated with the same multimodal strategy was reported. PATIENTS: The patients were treated with surgery, 2 courses of ifosfamide/carboplatin/etoposide(ICE), 2 courses of cyclophosphamide/etoposide/carboplatino/thiotepa (CECAT) or 2 other ICE courses, high dose chemotherapy (HDC) and radiotherapy. RESULTS: Eight patients underwent primary surgery achieving a complete removal in 3. Progressive disease (PD) occurred in 2/8 patients during ICE courses and in 3/4 during CECAT courses. After 4 courses 5 patients presented a PD. HDC was performed in 3 patients followed by local radiotherapy. The Kaplan Meier OS and EFS probability at 5 years are, respectively, 50% (CI 11-80%) and 33% (CI 6-66%). CONCLUSION: A strategy based on surgery, including a second surgical look, and on radiotherapy appears the best option. ICE regimen and HDC correlate with good prognosis in some patients but this approach needs further evaluation.

Antibiotic lock with vancomycin and urokinase can successfully treat colonized central venous catheters in pediatric cancer patients.

We used an antibiotic lock technique with vancomycin in combination with urokinase in 10 consecutive eligible children with Gram-positive catheter-related bacteremia persisting after appropriate intravenous antibiotics. Treatment was successful in sterilizing all colonized central venous catheters, avoiding device removal and delay of further chemotherapy. The antibiotic lock technique may represent a safe and effective therapeutic option in patients with selected, uncomplicated catheter-related bacteremias resistant to systemic antimicrobial therapy, particularly when maintaining a venous access is mandatory.

Short topotecan-based induction regimen in newly diagnosed high-risk neuroblastoma.

PURPOSE: Topotecan is an active drug in relapsed neuroblastoma. We investigated the efficacy and toxicity of a topotecan-based induction regimen in newly diagnosed neuroblastoma. METHODS: Patients older than 1 year with either metastatic or localised stage 2-3 MYCN-amplified neuroblastoma received 2 courses of high-dose topotecan (HD-TPT) 6mg/m(2) and high-dose cyclophosphamide (HD-CPM) 140 mg/kg, followed by 2 courses of ifosfamide, carboplatin and etoposide (ICE) every 28 days. After surgery on primary tumour, a fifth course with vincristine, doxorubicin and CPM was given, followed by high-dose chemotherapy with stem cell support. Response was assessed in accordance with the International Neuroblastoma Response Criteria. RESULTS: Of 35 consecutive patients, 33 had metastatic disease. The median length of induction phase was 133 days (range 91-207) and time to high-dose chemotherapy was 208 days (range 156-285). The median tumour volume reduction was 55% after two HD-TPT/HD-CPM courses and 80% after four courses. Radical surgery was performed in 16/27 patients after chemotherapy. After the fifth course, 29/34 patients (85%) had achieved a partial remission (12) or a CR/very good partial remission (17). CR of metastases was achieved in 13/32 (41%) and bone marrow was in complete remission in 16/24 patients (67%). Grade 4 neutropenia and/or thrombocytopenia occurred in 100% of HD-TPT/HD-CPM and in 95% of ICE courses, while non-haematological toxicities were manageable. CONCLUSIONS: These data indicate that our induction regimen is feasible and well tolerated. A major response rate of 85% with 41% complete metastatic response confirms this regimen as effective induction in high-risk neuroblastoma.

Prolonged response to oral gefitinib, cyclophosphamide, and topotecan in heavily pretreated relapsed stage 4 neuroblastoma: a case report.

A girl with metastatic neuroblastoma diagnosed at 4 years of age experienced an early disseminated relapse after high-dose chemotherapy. After reinduction, compassionate treatment with gefitinib (250 mg/d fixed dose) with oral topotecan (0.8 mg/m(2)/d) and cyclophosphamide (50 mg/m(2)/d) for 14 consecutive days, each course repeated every 28 days, was administered. Complete marrow clearance and metaiodobenzylguanidine response were achieved after 4 courses. After the first course, topotecan and cyclophosphamide were reduced by 25% for grade 4 hematologic toxicity. Subsequent courses were well tolerated. The girl remained progression free for 27 months. This combination may represent a viable therapeutic option and deserves further evaluation in resistant neuroblastoma.

High histologic and overall response to dose intensification of ifosfamide, carboplatin, and etoposide with cyclophosphamide, doxorubicin, and vincristine in patients with high-risk Ewing sarcoma family tumors: the Bambino Gesù Children's Hospital experience.

BACKGROUND: Ewing sarcoma (ES) and extraosseous ES/primitive neuroectodermal tumors (PNET) share histopathologic features of the ES family of tumors (ESFT). The authors report on their results from a regimen of ifosfamide, carboplatin, and etoposide (ICE) with cyclophosphamide, doxorubicin, and vincristine (CAV) dose intensification in patients with high-risk ESFT. METHODS: Since 1990, patients with ESFT and with 1 or more of the following risk factors were reviewed: tumor volume > 200 mL, tumor site with a poor prognosis, and pulmonary and/or bone marrow metastases. RESULTS: Thirty-six patients with ESFT who were involved in the study were divided into 2 arms of 18 patients each. One group received treatment with various regimens, and the other group received treatment with ICE plus CAV. The disease was brought under control more rapidly in the latter patients, for whom surgery was more easily feasible, and up to 90% of patients achieved a major response, with an estimated 3-year overall survival rate of 67% +/- 12%. CONCLUSIONS: The current results showed that ICE plus CAV was tolerated well and was effective in the studied subset of tumors, indicating that dose intensification correlates with better disease control, a high percentage of necrosis, and conservative surgery in patients with high-risk ESFT.