High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy.

Pinkerton, CR; Pritchard, Jon; Spitz, Lewis

doi:10.1200/jco.1986.4.2.194

Cited by 65 publications

(25 citation statements)

References 14 publications

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“…However, our data showed that chemotherapy regimen was not a significant predictor in FIGO stage I patients. In FIGO stage I, VAC produced a high proportion of cures, but in patients with metastatic disease the sustained remission rates of cisplatin-based chemotherapies are better than that of VAC (Pinkerton et al, 1986;Williams et al, 1989;Gershenson et al, 1990). Therefore, our results of multivariate analysis in FIGO stage I patients are not consistent with other reports concerning chemotherapy for ovarian YST.…”

Section: Clinicalfindingscontrasting

confidence: 56%

“…However, a combination of cisplatin, etoposide and bleomycin (BEP) (Smales & Peckman, 1987;Pinkerton et al, 1986;Gershenson et al, 1990;Williams et al, 1989) or cisplatin, vinblastine and bleomycin (PVB) (Bradof et al, 1982;Taylor et al, 1985;Einhorn & Donohue, 1977;Julian et al, 1980;Carlson et al, 1983;Davis et al, 1984) has been found to be even more effective and has produced remissions in patients with advanced-stage disease and in patients in whom other combinations of multiagent chemotherapy have failed (Bradof et al, 1982;Taylor et al, 1985;Einhorn & Donohue, 1977;Julian et al, 1980;Carlson et al, 1983;Davis et al, 1984;Smales & Peckman, 1987;Pinkerton et al, 1986;Williams et al, 1989;Gershenson et al, 1990). Cisplatin-based combination chemotherapy has revolutionised the treatment of patients with yolk sac tumour.…”

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confidence: 99%

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Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary

Sasaki

Furusato²,

Teshima³

et al. 1994

Br J Cancer

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Section: Clinicalfindingscontrasting

confidence: 56%

mentioning

confidence: 99%

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary

Sasaki

Furusato²,

Teshima³

et al. 1994

Br J Cancer

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“…This study demonstrates that, after cisplatin and carboplatin treatment the drug-target interaction is determined by both pharmacokinetic and, predominantly, cellular factors. Intrinsic differences between the two complexes, primarily reactivity, probably explain the lower adduct levels observed after carboplatin treatment.Keywords: cisplatin; carboplatin; Pt-DNA adduct; pharmacokinetics; child cancer Cisplatin and carboplatin are widely used in the treatment of solid tumours in childhood (Pinkerton et al, 1986;Pearson et al, 1992;Doz and Pinkerton, 1994). The activity and toxicity of cisplatin and carboplatin depend upon both pharmacokinetic and pharmacodynamic factors.…”

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confidence: 99%

“…Keywords: cisplatin; carboplatin; Pt-DNA adduct; pharmacokinetics; child cancer Cisplatin and carboplatin are widely used in the treatment of solid tumours in childhood (Pinkerton et al, 1986;Pearson et al, 1992;Doz and Pinkerton, 1994). The activity and toxicity of cisplatin and carboplatin depend upon both pharmacokinetic and pharmacodynamic factors.…”

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confidence: 99%

Platinum-DNA adduct formation in leucocytes of children in relation to pharmacokinetics after cisplatin and carboplatin therapy

Peng

Tilby²,

English³

et al. 1997

Br J Cancer

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Summary Platinum (Pt)-DNA adducts were measured in peripheral blood leucocytes (PBLs) from 24 children with solid tumours after standard cisplatin and/or carboplatin treatment. The relationship between Pt-DNA adduct levels and pharmacokinetics of cisplatin and carboplatin was investigated. Adduct measurements were performed by competitive enzyme-linked immunosorbent assay (ELISA) and plasma unbound Pt concentrations were measured by atomic absorption spectrophotometry (AAS). There was considerable interindividual variation in Pt-DNA adduct level that was weakly correlated (r 2 = 0.32) with the area under the unbound drug concentration vs time curve (AUC) at 6 h after the start of cisplatin infusion, indicating that the variation in Pt-DNA adduct levels was primarily determined by factors other than AUC. No clear relationship between AUC and adduct levels was seen at 24 and 48 h after cisplatin or at 6, 24 or 48 h after carboplatin. Carboplatin produced lower levels of immunoreactive adducts than did cisplatin (1.3±0.6 nmol Pt g-1 DNA vs 3.2 ± 1.7 nmol Pt g-' DNA), despite a 20-fold higher unbound drug AUC for carboplatin (8.0 ± 3.5 mg ml-' min vs 0.4 ± 0.2 mg ml-' min). This study demonstrates that, after cisplatin and carboplatin treatment the drug-target interaction is determined by both pharmacokinetic and, predominantly, cellular factors. Intrinsic differences between the two complexes, primarily reactivity, probably explain the lower adduct levels observed after carboplatin treatment.Keywords: cisplatin; carboplatin; Pt-DNA adduct; pharmacokinetics; child cancer Cisplatin and carboplatin are widely used in the treatment of solid tumours in childhood (Pinkerton et al, 1986;Pearson et al, 1992;Doz and Pinkerton, 1994). The activity and toxicity of cisplatin and carboplatin depend upon both pharmacokinetic and pharmacodynamic factors. A number of clinical pharmacokineticpharmacodynamic relationships have been described for cisplatin (Campbell et al, 1983;Reece et al, 1987;Thomas et al, 1994) and carboplatin (Egorin et al, 1984;Newell et al, 1987Newell et al, , 1993Harland et al, 1991;Horwich et al, 1991;Sorensen et al, 1991;Jodrell et al, 1992), and interpatient variability in tumour response to and/or tolerance of platinum (Pt)-complex therapy may relate to plasma levels more closely than to dose. Therefore optimum treatment with Pt drugs may necessitate adjustment for interindividual pharmacokinetic differences. Renal function-based dosing formulae have been developed for carboplatin administration to children (Marina et al, 1993;Newell et al, 1993;Chatelut et al, 1996) because carboplatin is cleared primarily by glomerular filtration.Although pharmacokinetics is one determinant of the clinical efficacy of Pt complexes, intracellular factors are certain to play an additional role. Pt complexes exert their anti-tumour effect by reacting with DNA (Roberts and Thomson, 1979;Sherman and Lippard, 1987;Fichtinger-Schepman et al, 1995 (Poirier et al, 1982;Fichtinger-Schepman et al, 1985;Terheggen et al, 1988; Tilby...

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“…Dramatic improvement in cure rates of adults with malignant germ cell tumours using cisplatin-based regimens have been mirrored in paediatric practice (Einhorn & Donohue, 1977;Peckham et al, 1983;Williams et al, 1987;Pinkerton et al, 1986;Mann et al, 1987). With short-duration chemotherapy, non-mutilating surgery and avoidance of radiotherapy or alkylating agents, the majority of children, including many with metastatic MGCT, can be cured.…”

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confidence: 99%

'JEB' – a carboplatin based regimen for malignant germ cell tumours in children

Pinkerton

Broadbent²,

Horwich³

et al. 1990

Br J Cancer

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(Brock et al., 1988;Koliouskas et al., 1985), there is little evidence that either renal function or hearing loss shows meaningful improvement with time.Substitution for cisplatin by a less toxic analogue such as carboplatin has been shown to be effective in ovarian cancer (Calvert et al., 1982;Wiltshaw et al., 1985) and this drug has clear activity in adult Phase II studies with MGCT (Horwich et al., 1988). There is, however, little or no evidence that significant non-cross resistance exists in cisplatin-resistant tumours and its use in the JEB regimen is primarily to avoid toxicity. In this regimen, carboplatin is given at a dose based on renal function calculated from the Calvert formula (Calvert et al., 1989). This is predicted to produce an area under the drug concentration curve (AUC) which may lead to significant but manageable myelosuppression but possibly maximum therapeutic effect. Early studies in adults show clearly that inferior results are achieved with carboplatin unless the dose is pushed to myelosuppressive levels .Etoposide and bleomycin are used as in the standard BEP regimen (Peckham et al., 1983). There is some controversy about the necessity of weekly rather than 3-weekly bleomycin. In this study, if it was possible to monitor lung function, children were given this drug weekly. Infants, whose lung function could not be tested, received bleomycin 3-weekly after the first two cycles of chemotherapy. Patients and methodsTwenty-one children aged 1 to 16 years (median 11 years) received the JEB regimen. Nineteen were previously untreated and two had received single courses of PVB and BEP chemotherapy respectively. Clinical details are shown in Table I. Serum markers (a-fetoprotein and P-HCG) were estimated in all patients by immunoassay. Staging investigations included PA and lateral chest X-ray, CT chest scan, isotope bone scan and abdominal ultrasound or CT scan. Lymphography was not performed.Indications for chemotherapy were the presence of metastatic disease in lung (6), lymph nodes (6), or peritoneum (1); bulky, unresectable primary tumour (5), peritoneal spill at surgery (3), or an intracranial primary (2). The testis was the primary site in 6 patients, ovary in 8 and sacrococcygeal area in 4. A one-year-old infant with a large vaginal tumour was treated electively with chemotherapy alone to avoid mutilating surgery. One boy with a pineal germinoma received JEB after complete resection and before irradiation. A second patient with a pineal tumour had undergone surgery but developed rapidly progressive disease within a month of this. a-FP was elevated in 19 patients, P-HCG in 8. In no patient was both x-FP and P-HCG normal. The chemotherapy is outlined in Figure 1. Bleomycin (15 mg m-2) was given weekly as a slow intravenous infusion. Etoposide (120 mg m2) was administered daily x 3 as a 1 to 3 hour infusion and carboplatin infused over one hour. The formula for calculating the dose of carboplatin was based on the uncorrected "Cr-EDTA clearance. In four children the GFR was not measured ...

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High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy.

Cited by 65 publications

References 14 publications

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary

Platinum-DNA adduct formation in leucocytes of children in relation to pharmacokinetics after cisplatin and carboplatin therapy

'JEB' – a carboplatin based regimen for malignant germ cell tumours in children

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