Results of the United Kingdom children's cancer study group's malignant germ cell tumor studies

Abstract

The United Kingdom Children's Cancer Study Group's malignant germ cell tumor studies were undertaken to establish standard protocols for investigating, staging, and treating children, and to study the efficacy of new drug combinations and the value of serial measurement of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG). Boys with Stage I testicular tumors were treated by orchidectomy alone, whereas, after appropriate surgery, chemotherapy was recommended for children with more advanced testicular tumors or with tumors at other sites. From 1979 to 1987, 126 children aged 0 to younger than 16 years with malignant germ cell tumors were registered. They were similar to patients in other large pediatric series with respect to sites of origin, age at presentation in relationship to primary site, histology, female predominance for sacrococcygeal site, and presence of associated malformations (present in 17%). Serum AFP was measured in 123 patients and was elevated in 115, whereas HCG was raised in 19 of 77. Monitoring by serial AFP measurement proved valuable in assessing response to therapy and in early detection of tumor recurrence. When treatment results were assessed in February 1988, 101 of 122 patients were alive (four who received nonprotocol chemotherapy were excluded). Forty-four patients had been cured by surgery alone (41 with testicular tumors, two with ovarian tumors, and one with sacrococcygeal tumor). All of the remaining 78 children received chemotherapy. The initial low dose vincristine, actinomycin, and cyclophosphamide (LDVAC) regimen proved ineffective, actuarial survival at 5 years followup being 8% (12 patients), and a regimen of cisplatin, vinblastine, and bleomycin (PVB) caused unacceptable toxicity, with actuarial survival at 5 years follow-up being 67% (nine patients). Five-year actuarial survival was 87% for 17 children given high dose VAC with or without doxorubicin and 84% for 33 given bleomycin, etoposide, and cisplatin (BEP). All 7 children given various combinations of these regimens survived. Excluding the 12 LDVAC cases, patient survival by site was as follows: testis (59 patients, 100%); vagina, uterus, and prostate (four patients, 100%); ovary (25 patients, 88%); thorax (five patients, 40%), and other (four patients, 67%). Similarly, patient survival by stage was Stage I (62,97%), Stage II (14,86%); Stage III (18,83%); and Stage IV (16,72%). Survival by histology was analysed only in cases for which histologic review had been done the LDVAC cases were excluded.(ABSTRACT TRUNCATED AT 400 WORDS)

Amifostine does not protect against the ototoxicity of high‐dose cisplatin combined with etoposide and bleomycin in pediatric germ‐cell tumors

“…[5][6][7][8][9]38,39 Significant concerns regarding the longterm toxicity of cisplatin and bleomycin [11][12][13][14][15] delayed the introduction of cisplatin-based therapy in pediatric patients. After pediatric Phase II studies suggesting that high-dose cisplatin was effective and tolerable in patients with solid tumors and neuroblastoma, 23,24 the POG/CCG Intergroup Germ-Cell Tumor Subcommittee designed a randomized study to evaluate the effect of cisplatin dose intensity on outcome.…”

“…6 -9 Although small pediatric trials suggested cisplatin-based therapy was efficacious, 10 there were significant concerns regarding the long-term toxicity of this agent in young children. [11][12][13][14][15] Based on these concerns, several pediatric investigators evaluated the use of other strategies to eliminate the toxicity associated with cisplatin. Mann et al 16 evaluated the use of carboplatin, etoposide, and bleomycin (JEB) in pediatric patients with malignant GCT and reported a 5-year event-free survival (EFS) of 87.8%.…”

Trends in survival for childhood cancer in Britain diagnosed 1971-85

“…The role of chemotherapy in ovarian tumours during the first half of the study period has been previously described (La Vecchia et al, 1983). The improvements in more recent years were parallel with those in the UKCCSG germ-cell tumour studies (Mann et al, 1989), in which many of the children analysed here were entered.…”

Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours

“…Therefore, germ cell malignancies arising from extragonadal primary site represent nearly 50 -60% of all GCTs in children . Extragonadal primary location coupled with high serum levels of alpha-fetoprotein (AFP) (more than 10 000 ng ml À1 ) at diagnosis are the most unfavourable prognostic factors for these children (Mann et al, 1989;Marina et al, 1992;Baranzelli et al, 1999Baranzelli et al, , 2000Schneider et al, 2000;Lo Curto et al, 2003). Moreover, the prognosis of extragonadal GCT is significantly influenced by the histological differentiation, with the secreting GCTs (embryonal carcinoma, yolk sac tumour, choriocarcinoma) and immature teratoma having a higher risk of relapse after primary treatment than germinoma/dysgerminoma and mature teratoma .…”