Liane Lockwood

Postoperative Chemotherapy in Children Less Than 4 Years of Age with Malignant Brain Tumors: Promising Initial Response to a Vetopec-based Regimen A Study of the Australian and New Zealand Children's Cancer Study Group (anzccsg)

Purpose: Postoperative chemotherapy with indefinite postponement of radiation therapy in children <4 years old with brain tumors was investigated in a multi-institutional study. Patients and Methods: From 1991 to 1995. 42 patients aged 3 to 47 months (median 20) with brain tumors were enrolled in a 2-phase chemotherapy protocol: 16 patients had medulloblastoma (MB); 8 had supratentorial primitive neuroectodermal tumor (PNET); 14 had ependymoma; and 4 had other tumors. The initial phase was comprised of 4 courses of the 3-drug regimen: vineristine (VCR), etoposide (VP-16). and intensive cyclophosphamide (CPA) in a previously reported schedule (VFTOPEC). The continuation phase was comprised of 2-drug courses: A. CPA + VCR: B. cisplatin + VP-16; and C. carbopfatin + VP-16, for a total duration of 64 weeks. Results: Response to VETOPFC was evaluable in 28 patients with postresection residual (25) and/or metastatic (1 M2, 6 M3) tumor. There were 9 complete responses (CR) and 9 partial responses (PR) with a combined CR + PR of 64% (95% confidence interval [CI] 44 to 81). In 12 evaluable patients with MB, CR + PR was 82% (48 to 98); in 6 patients with PNET. 50% (12 to 88); and, in 8 patients with ependymoma. 86% (42 to 99). Of 40 patients eligible for further analysis, 6 remain progressionfree at a median of 30 months, 14 are alive at a median of 38 months. 29 have progressed at a median of 7 months (range. 2 to 37 months), and 26 have died. The progression-free and overall survival rates at 36 months are estimated to be 11% (95% CI 1 to 22) and 34% (18 to 50). respectively. Conclusions: The initial response to the VETOPEC regimen is encouraging and warrants study of further dose escalation. Survival remains poor with current strategies in this high-risk population.

Autologous bone marrow transplantation for advanced neuroblastoma using teniposide, doxorubicin, melphalan, cisplatin, and total-body irradiation.

BACKGROUND Disseminated neuroblastoma after infancy has a dismal prognosis; long-term survival with conventional therapy occurs in approximately 10% of cases. PATIENTS AND METHODS Between 1985 and 1992, we followed a strategy aimed to achieve remission with an induction combination of intensive chemotherapy, primary resection, and tumor-bed radiotherapy (TBRT). Patients who achieved remission proceeded to myeloablative chemoradiotherapy and unpurged autologous bone marrow transplant (ABMT). Twenty-eight patients older than 1 year presented with stage IV disease during the study period; six died of progressive disease and three died of complications of therapy. Nineteen patients achieved remission, two of whom did not receive ABMT. Seventeen patients proceeded to ABMT. Conditioning was with teniposide 130 mg/m2, doxorubicin 30 mg/m2, melphalan 120 mg/m2, cisplatin 80 mg/m2, and total-body irradiation 12 Gy in six fractions (modified VAMP-TBI). RESULTS Principal nonhematologic toxicities were mucositis and diarrhea. There were no ABMT-related deaths. Two patients relapsed at 8 and 26 months post-ABMT, respectively. Fifteen patients remain in complete remission (CR) at 24 to 102 months (median, 71) from ABMT and 30 to 114 months (median, 78) from diagnosis. Survival rates of all 28 patients are 61% and 50% at 2 and 5 years, respectively, and the disease-free survival (DFS) of the ABMT group is 94% and 87% at 2 and 5 years, respectively. CONCLUSION Modified VAMP-TBI appears to be an effective conditioning regimen, with 15 of 17 patients remaining disease-free, with no toxic deaths. This result compares favorably with that of other groups. Larger numbers of patients need to be treated to confirm the efficacy of this therapy.

Dose-intensive cyclophosphamide with etoposide and vincristine for pediatric solid tumors: a phase I/II pilot study by the Australia and New Zealand Childhood Cancer Study Group.

PURPOSE This pilot study of the Australia and New Zealand Childhood Cancer Study Group investigated the effectiveness and toxicity of a regimen incorporating vincristine (VCR), etoposide, and divided-dose, escalating cyclophosphamide (CPA) (VETOPEC) in 23 patients aged 1 to 20 years with solid tumors. PATIENTS AND METHODS Seventeen patients (group A) had recurrent or refractory tumors after prior multiagent therapy, and six patients (group B) with adverse prognostic indicators were treated at initial presentation. Treatment cycles were 21 to 28 days and consisted of vincristine (0.05 mg/kg) on days 1 and 14, with etoposide (2.5 mg/kg/d) plus escalating CPA on days 1, 2, and 3. The CPA dosage was escalated from 30 mg/kg/d in cycle no. 1 by 5 mg/kg/d in each cycle to a maximum of 55 mg/kg/d in cycle no. 6. RESULTS Of 20 patients assessable for tumor response, 19 (95%) responded after two to six cycles of VETOPEC: seven complete responses (CRs); eight very good partial responses (VGPRs); and four partial responses (PRs). In group A, 13 of 14 (93%) assessable patients responded (five CRs, four VGPRs, four PRs), and in group B, five stage IV and one stage III patient achieved two CRs and four VGPRs. The principal toxicity was myelosuppression. Grade IV neutropenia occurred after 98% of cycles, and the incidence of grade IV thrombocytopenia increased from 37% after cycle no. 1 to 91% after cycle no. 6 (P = .002). A total of 115 cycles delivered were followed by 62 febrile admissions (54%), and showed a significant rise with increasing cycles (P = .001). One patient died of septicemia. CONCLUSION This combination and scheduling produced a high response rate in patients with recurrent, refractory, or advanced solid tumors of childhood. Further studies of this regimen and of strategies to reduce hematologic toxicity are warranted.

Activity of postoperative carboplatin, etoposide, and high-dose methotrexate in pediatric CNS embryonal tumors: results of a phase II study in newly diagnosed children.

Background Chemotherapy is used as an alternative to irradiation or to minimize the irradiation exposure among infants with medulloblastoma or other CNS embryonal tumors. Adjuvant chemotherapy is commonly used in older children with high-risk medulloblastoma to improve survival or to allow a reduction in the craniospinal irradiation dose in standard-risk patients. However, optimal multimodality therapy, including the precise role of chemotherapy, has not been defined for these groups of patients. The objective of the present study is to assess the efficacy and toxicity of four postoperative courses of carboplatin, etoposide, and high-dose methotrexate in newly diagnosed children with medulloblastoma or other CNS embryonal tumors. Procedure Twenty-eight children, aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19), supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative chemotherapy comprised carboplatin 350 mg/m2 and etoposide 100 mg/m2 on Days 1 & 2, and methotrexate 8 g/m2 on Day 3, repeated at 21–28-day intervals for a total of four courses. Therapy following completion of the initial Phase II study was influenced by patient age and investigator preference. Results The combined complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9 and PR, 6/9), and for all patients it was 79%. Patients aged  3 years. Treatment was well tolerated although myelosuppression and thrombocytopenia were common. Conclusions The combination of carboplatin, etoposide, and high-dose methotrexate is highly active in pediatric patients with CNS embryonal tumors. Med Pediatr Oncol 2002;39:168–174.

Videophone support for an eight-year-old boy undergoing paediatric bone marrow transplantation

We report the use of an Internet-based videophone to support a child undergoing bone marrow transplantation (BMT). Over the Christmas period, an eight-year-old boy with an underlying diagnosis of attention-deficit/hyperactivity disorder (ADHD) and a history of absconding and aggressive non-compliant behaviour was treated by BMT. We installed an Internet-based videophone in the patients hospital room two days post-transplant. A second videophone was installed in the patients home and used the existing home telephone line. In all, 14 videophone calls were made over a nine-day period. The videophone improved interfamily social and emotional support, and appeared to reduce some of the inherent anxiety and distress resulting from paediatric bone marrow transplantation.

Understanding parents and adolescents' perception of a research clinical trial and the informed consent/assent process in the paediatric oncology setting

Purpose: To estimate five-year survival and the proportion of patients ‘cured’ of acute myeloid Leukaemia (AML) and the survival of the ‘uncured’ by age at diagnosis, and to compare estimates for England with those observed in Sweden. Method: This population-based study included records of 47,250 adult patients within the National Cancer Registry who were diagnosed with AML in England during 1971–2006. Relative survival and cure mixture models were used to produce estimates and predictions of outcome. Results: Five-year survival and the proportion ‘cured’ increased for those under the age of 70 years at diagnosis during 1971–2006, but the magnitude of the increase varied with age. Increasing age at diagnosis was associated with poorer outcome. The most dramatic increase in five-year survival occurred in those aged 15–24 years, from 7% to 50%, but for those over the age of 70 years it remained less than 5%. The proportion ‘cured’ is predicted to increase to 46% for those aged 15–24 years and 13% for those aged 60–69 years at diagnosis in 2006. The median survival of the ‘uncured’ increased from 0.41 years in 1975 to 0.93 years in 2000 in those aged 15–24 years, and from 0.19 years to 0.38 years in those aged 60–69 years at diagnosis.Conclusion: Improvements in the long-term outcome of patients with AML have been agedependant, with dramatic improvements seen in those diagnosed under the age of 25 years. Whilst these improvements are welcome, long-term outcome of adults with AML in England is still poorer than in Sweden, especially in those under the age of 40 years.

Activity of postoperative carboplatin, etoposide, and high‐dose methotrexate in pediatric CNS embryonal tumors: Results of a phase II study in newly diagnosed children

Background Chemotherapy is used as an alternative to irradiation or to minimize the irradiation exposure among infants with medulloblastoma or other CNS embryonal tumors. Adjuvant chemotherapy is commonly used in older children with high-risk medulloblastoma to improve survival or to allow a reduction in the craniospinal irradiation dose in standard-risk patients. However, optimal multimodality therapy, including the precise role of chemotherapy, has not been defined for these groups of patients. The objective of the present study is to assess the efficacy and toxicity of four postoperative courses of carboplatin, etoposide, and high-dose methotrexate in newly diagnosed children with medulloblastoma or other CNS embryonal tumors. Procedure Twenty-eight children, aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19), supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative chemotherapy comprised carboplatin 350 mg/m2 and etoposide 100 mg/m2 on Days 1 & 2, and methotrexate 8 g/m2 on Day 3, repeated at 21–28-day intervals for a total of four courses. Therapy following completion of the initial Phase II study was influenced by patient age and investigator preference. Results The combined complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9 and PR, 6/9), and for all patients it was 79%. Patients aged  3 years. Treatment was well tolerated although myelosuppression and thrombocytopenia were common. Conclusions The combination of carboplatin, etoposide, and high-dose methotrexate is highly active in pediatric patients with CNS embryonal tumors. Med Pediatr Oncol 2002;39:168–174.