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Biomedical subjects

C R Pinkerton

Publications and source records attributed to C R Pinkerton.

At least 19 recordsLinked to original sources
PubMed1992

High-dose methylprednisolone sodium succinate as a single agent in relapsed childhood acute lymphoblastic leukaemia.

Twenty children received methylprednisolone (1 g/m2), daily for 5 to 8 days, as initial single agent therapy for relapsed acute lymphoblastic leukaemia. Bone marrow blasts were reduced to less than 5% in 2 and 5-10% in 3 of 12 patients with bone marrow relapses. In 3/9 with central nervous system relapses the cerebrospinal fluid (CSF) blasts completely cleared and were reduced in 4 others. In two patients with testicular relapses there was shrinkage of tumour and one patient with a navicular bone relapse became pain free. Toxicity was minimal. These results indicate high-dose methylprednisolone is an effective agent, particularly in the treatment of established central nervous system (CNS) disease and could contribute to early CNS directed therapy in acute lymphoblastic leukaemia.

Administration, Oral↗
PubMed1992

Seizures and cortical dysfunction following high-dose cisplatin administration in children.

Four of eight children with advanced neuroblastoma treated with a rapid delivery high dose intensity cisplatin based regimen developed acute neurological toxicity. Three had seizures and one developed transient blindness. In the absence of other causes it seems probable that high dose cisplatin (200 mg/m2) as a continuous infusion over five days followed 10 days later by 80 mg/m2 infused over 48 hours was responsible. Other risk factors included an associated deterioration in renal function and neutropenia related fever.

Adrenal Gland Neoplasms↗
PubMed1992

Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis.

This is a retrospective analysis of children with metastatic soft tissue sarcoma (STS) registered in the major European STS studies: the SIOP MMT 75, the German CWS 1981 and 1986 studies, the Italian STS study, and the United Kingdom Children's Cancer Study Group centres in Britain. One hundred forty-six patients out of 164 were evaluable in this analysis. The median age was 7 years (1-18) and the male/female ratio was 1.3:1. The median follow-up was 80 months (7-171). The most common site of the primary tumor was the extremity (28%), which correlated well with the high preponderance (39%) of the alveolar type of RMS (aRMS). There was no dominant combination of metastatic sites and the most common single organ with metastasis was the lung (41%). Since the therapy depended on the country and period in which the patient was treated, we did not analyse the outcome and therapy together. Complete remission was achieved in 50% of the cases. Those with aRMS had a good chance of achieving CR (61%) but the majority of these patients relapsed (78%). The median time needed to relapse was 243 days (53 days to 47 months) for all patients. Analysis of the site of the primary tumor showed that the CR rate was best in the GU non-BP site (62%) and worst in PM cases (35%). The overall survival and DFS rate were 18% and 15%, respectively. The GU non-BP patients had a DFS rate of 50%, while the rate for all other sites varied between 12% and 18%. A total of 24 patients remained in CCR. The majority of them had embryonal type of RMS and metastases in only one anatomic site. Our analysis indicates that the best chance of prolonged survival was in metastatic GU non-BP cases, patients with embryonal type RMS, and those with metastases in only one organ. To try to improve the treatment of metastatic STS, a prospective European cooperative study was started in 1989.

Adolescent↗
PubMed1992

High-dose rapid schedule chemotherapy for disseminated neuroblastoma.

In a high-dose schedule for disseminated neuroblastoma, eight courses of chemotherapy were administered every 10 days, regardless of myelosuppression, to eradicate tumour cells rapidly and reduce emergence of drug-resistant clones. Relatively non-myelotoxic vincristine and cisplatin were alternated with high-dose cisplatin-etoposide and cyclophosphamide-etoposide. Of 12 evaluable patients, there were 1 complete (CR), 3 very good partial (VGPR), 5 partial (PR) and 3 mixed responses (MR) 100 days after starting treatment. 6 out of 9 achieved a bone marrow CR at 40 days. 9 of 11 primary tumours were completely resected, after which 4 patients had CR, 3 VGPR (bone scan alone being abnormal), 4 PR and 1 mixed response (MR). Myelotoxicity was the major adverse effect. The only death was due to fungal infection. Clinically important renal dysfunction occurred in 3 patients. 4 had convulsions and 4 temporary hypertension. This schedule produced a rapid response and its toxicity, though serious, was manageable. Further evaluation is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Pilot study of a rapid etoposide-cisplatin regimen in paediatric soft tissue sarcomas.

10 patients with refractory or relapsed soft tissue sarcoma were treated with weekly etoposide (150 mg/m2 on days 1, 2 and 3) and cisplatin (60 mg/m2 on day 2). Toxicity was mainly myelosuppression which resulted in deviation from planned weekly chemotherapy scheduling. With this rapid dose-delivery schedule the tolerated median dose intensities were 161 mg/m2 per week for etoposide and 49 mg/m2 per week for cisplatin. In 9 evaluable patients there were 7 responses, 2 complete and 5 partial, giving a response rate of 78% (confidence interval 51-100%). The combination of etoposide and cisplatin in this schedule produced a higher response rate than reported with previous schedules and is worthy of further evaluation.

Adolescent↗
PubMed1992

'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae.

In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients.

Adolescent↗
PubMed1992

Treatment of advanced stage T cell lymphoblastic lymphoma: results of the United Kingdom Children's Cancer Study Group (UKCCSG) protocol 8503.

Ninety-five unselected patients with stage III and IV T cell lymphoblastic lymphoma were treated according to the United Kingdom Children's Cancer Study Group protocol 8503. This was a continuous, intensive leukaemia type regimen including cranial irradiation (18 Gy in 10 fractions) and continuing chemotherapy for 2 years identical to the concurrent Medical Research Council ALL protocol. Four-year event-free survival was 65% (95% CI 50-80%) with no significant difference between stage III and stage IV cases. 4.2% of patients died of infection or non-tumour related events. Following relapse salvage was unlikely without high dose chemotherapy and bone marrow rescue. These results show an improvement over previous U.K. studies but we need to continue to search for subsets of patients with resistant disease for whom even more intensive therapy possibly combined with bone marrow rescue is required.

Adolescent↗
PubMed1992

Ewing sarcoma: MR imaging of chemotherapy-induced changes with histologic correlation.

In a study group of 18 consecutive patients with Ewing sarcoma proved by means of biopsy, the signal intensity characteristics of tumor on magnetic resonance (MR) images were assessed before and after chemotherapy. Sixteen patients underwent MR imaging at 1.5 T before chemotherapy; all 18 patients underwent MR imaging at 1.5 T within 10 days after chemotherapy. Standard spin-echo sequences were used with T1 and T2 weighting in all patients. The primary tumor was visualized in all 16 patients who underwent MR imaging before chemotherapy. Histologic correlation, obtained in 14 patients, showed that areas of high T2-weighted signal intensity on MR images obtained after chemotherapy may represent tumor necrosis, cystic hemorrhagic areas, and fibroblastic repair tissue. In 10 patients (71%), microscopic clusters of viable tumor cells were depicted in areas of both low and high signal intensity after treatment. It is concluded that MR imaging is unreliable for exclusion of active disease, although a pattern of change in signal intensity is qualitative evidence of chemotherapeutic effect.

Adolescent↗
PubMed1991

Response rates in relapsed Wilms' tumor. A need for new effective agents.

Three hundred eighty-one children with Wilms' tumor were treated in the United Kingdom Children's Cancer Study Group WT1 Study (1982 to 1986). Seventy-one patients had relapses during or after treatment with surgery and chemotherapy, and radiation therapy, depending on stage and histologic characteristics. Forty-nine patients were evaluable for disease response to second-line chemotherapy alone. Evaluation of response to chemotherapy was impossible in the remaining patients because either surgery or radiation therapy was used at the time of relapse. With second-line combination chemotherapy (which included ifosfamide, etoposide/VM26, cisplatin/carboplatin, bleomycin, melphalan, and Thiotepa [Lederle Laboratories, Pearl River, NY]), there were five complete responses and 12 partial responses. In patients with favorable histologic findings, six of nine with Stage I, five of ten with Stage II, none of 11 with Stage III, three of 16 with Stage IV, and one of five with Stage V disease survived. Two survivors were treated with chemotherapy alone; the others received combined treatment with chemotherapy, radiation therapy, and/or surgery. For those with unfavorable histologic findings of any stage, only two of 20 survived. The authors conclude that, even for patients with localized disease with favorable histologic findings, the "salvage" rate is little more than 50%, and for all other stages and histologic findings the likelihood of cure after relapse is remote. There is clearly a need for additional effective chemotherapeutic agents for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cisplatin ototoxicity in children: a practical grading system.

A long-term follow-up study was carried out to assess ototoxicity in children who had been treated for a malignant tumour with "standard dose" cisplatin (60-100 mg/m2 per course), and were at least 2 years from stopping treatment. The median age at diagnosis was 2 years 2 months (range 1 month to 13.5 years). On the basis of hearing assessment by pure-tone audiometry, a practical grading system of hearing loss from 0 to 4 is proposed. Moderate to severe high-frequency hearing loss (grade 2-4) was found in half the children and 10 require appropriate hearing aids. The risk of developing ototoxicity increased significantly with the cumulative cisplatin dose (P = 0.027), although there was considerable individual susceptibility. Serial follow-up testing, to a median of 4 years after completion of cisplatin treatment, showed no recovery of hearing in any of these children. We suggest careful monitoring of young children by a consultant audiological physician throughout treatment with cisplatin, particularly when doses of 400 mg/m2 and over have been reached. Alternative chemotherapy should be discussed if grade 2 ototoxicity develops.

Adolescent↗
PubMed1991

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas.

Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV--12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non-metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Outcome in stage III non-Hodgkin's lymphoma in children (UKCCSG study NHL 86)--how much treatment is needed? United Kingdom Children's Cancer Study Group.

Forty-four children aged 3-13 years with Murphy stage III B cell non-Hodgkin's lymphoma were treated between May 1986 and December 1989. All have been followed up for at least 12 months. The primary site was the abdomen in 37 children, 24 of whom had involvement of other organs or nodal disease outside the abdomen. Twenty-eight received a standard dose regimen (regimen 1) and 16 had a more intensive regimen (regimen 2--MACHO). Fourteen patients (87%) who received MACHO had extensive multi-organ disease compared to 15 (53%) on regimen 1. Most of the latter had only pleural effusions. Thirty-four children are alive relapse free and considering the early relapse pattern in this disease are probably cured (actuarial event free survival = 76%). There has been one relapse (6%) after MACHO, but three toxic deaths. Six patients (21%) on the less intensive regimen have relapsed. Morbidity was high in terms of infection and need for haematological support and hospitalisation in the one third of children electively given the more intensive regimen. It is concluded that the vast majority of children with stage III disease who have disease limited to lymph nodes are curable with a moderately intensive regimen. Those with multiorgan involvement probably require more intensive treatment. It is therefore of importance to clarify prognostic factors in these patients to determine who can be cured with a less intensive regimen and who requires further dose intensification.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse.

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.

Adolescent↗