Use of CA-125 in Clinical Trial Evaluation of New Therapeutic Drugs for Ovarian Cancer

Rustin, G. J. S.; Bast, Robert C.; Kelloff, Gary J.; Barrett, J. Carl; Carter, Stephen K.; Nisen, Perry D.; Sigman, Caroline C.; Parkinson, David; Ruddon, Raymond W.

doi:10.1158/1078-0432.ccr-03-0787

Cited by 120 publications

(85 citation statements)

References 79 publications

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“…Response evaluation. Clinical response was assessed at the completion of 6 chemotherapy cycles (or after at least 3 completed cycles) via clinical, radiographic and serologic means in accordance with the WHO response criteria (19) and the Rustin criteria (20). Patients with residual disease at start of chemotherapy and who completed at least 3 cycles of chemotherapy (n=85) were evaluable for clinical response evaluation.…”

Section: Methodsmentioning

confidence: 99%

A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation

Sorbe

Graflund²,

Nygren³

et al. 2011

Int J Oncol

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Abstract. The purpose of this study was to assess the response rate, toxicity, progression-free survival (PFS) and overall survival (OS) in a series of advanced stage ovarian carcinoma patients treated with a first-line weekly docetaxel and three weekly carboplatin regimens. All eligible patients were treated with intravenous docetaxel (30 mg/m 2 ) on Days 1, 8 and 15, and carboplatin (area under the curve, 5) on Day 1; Q21 days for at least 6 cycles. Neurological tests, questionnaires, and the EORTC QLQ-C30 and OV28 were used for quality-of-life assessments. One hundred and six patients received at least one cycle of primary chemotherapy (median 6.0; range, 1-9) and they were evaluable for toxicity assessment. Eighty-five patients had evaluable disease and received at least 3 courses of chemotherapy and were evaluable for clinical response rate. The overall response rate was 78.8% (95% CI 70.1-87.5%) and the biochemical response was 92.8% (95% CI 87.2-98.4%). The median PFS was 12.0 months and the median OS was 35.3 months. Thirty-six patients (34.0%) experienced grades 3 and 4 neutropenia, which resulted in the removal of 3 patients. Six patients (5.7%) experienced grades 3 or 4 thrombocytopenia. No patients experienced grade 3-4 sensory neuropathy. Epiphora, nail changes and fatigue were frequently recorded non-hematological side effects. The tolerable hematological toxicity (no need for colony-stimulating factors) and the low rate of severe neurotoxicity (only grade 1-2) and response rates in line with the standard 3-week paclitaxel-carboplatin regimen for advanced primary ovarian carcinoma after suboptimal cytoreductive surgery make this regimen an interesting alternative in selected patients.

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Section: Methodsmentioning

confidence: 99%

A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation

Sorbe

Graflund²,

Nygren³

et al. 2011

Int J Oncol

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“…Objective responses were confirmed by repeat assessments after X4 weeks. Prostate-specific antigen (PSA) declines or rises were described in terms of the PSA working group criteria (Bubley et al, 1999) and CA-125 was measured in all ovarian cancer patients and described as a percentage change from baseline as described previously (Rustin et al, 2004). …”

Section: Tumour Assessmentsmentioning

confidence: 99%

A phase Ib study of pertuzumab, a recombinant humanised antibody to HER2, and docetaxel in patients with advanced solid tumours

et al. 2007

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Pertuzumab represents the first in a new class of targeted therapeutics known as HER dimerisation inhibitors. We conducted a phase Ib study to determine the maximum-tolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction of docetaxel when administered in combination with pertuzumab. Initially, two dose levels of docetaxel (60 and 75 mg m À2 ) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m À2 ) were explored in combination following a fixed dose of 420 mg of pertuzumab with a loading dose of 840 mg. Both drugs were administered intravenously every 3 weeks. The latter dose of pertuzumab was allowed after an amendment to the original protocol when phase II data suggesting no difference in toxicity or activity between the 2 doses became available. Two patients out of two treated at docetaxel 75 mg m À2 in combination with pertuzumab 1050 mg suffered DLT (grade 3 diarrhoea and grade 4 febrile neutropaenia). Two out of five patients treated at docetaxel 100 mg m À2 in combination with pertuzumab 420 mg with a loading dose of 840 mg suffered DLT (grade 3 fatigue and grade 4 febrile neutropaenia). Stable disease was observed at four cycles in more than half of the patients treated and a confirmed radiological partial response with a 450% decline in PSA in a patient with hormone refractory prostate cancer were observed. There were no pharmacokinetic drug -drug interactions. The recommended phase II dose of this combination was docetaxel 75 mg m À2 and 420 mg pertuzumab following a loading dose of 840 mg.

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“…15,16 These tests may be particularly useful in individuals who are asymptomatic, who also have no measurable tumor masses, and where there is a desire to learn if the antineoplastic agent being administered is actually producing a favorable impact on the malignant cell population.…”

Section: Examplementioning

confidence: 99%

“…16 However, as of this date the FDA has not permitted a documented rising serum CA-125 antigen level to be an acceptable endpoint for disease progression in ovarian cancer trials that are being conducted to secure regulatory approval of a new antineoplastic agent. Thus, currently a patient without other clinical or radiographic (eg, new computed tomography [CT] scan findings) evidence of progression being treated on such a study who experiences a rise in the CA-125 antigen level that would satisfy acceptable criteria for progression (as defined by data in the peer-reviewed literature and widely accepted in the academic gynecologic cancer community) 17 would either be required to continue treatment or, if removed from the study, would be considered a ''protocol violation.''…”

Section: Examplementioning

confidence: 99%

Informing prospective research subjects of the influence of regulatory requirements for drug approval on the design of clinical trials in oncology

Markman

2007

Cancer

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An established tenet of ethical clinical research stipulates that individuals considered for entry into therapeutic trials must be provided with all data that might influence their decision. However, discussion in the literature regarding the investigators' responsibility to inform possible participants about the nature and impact of regulatory requirements on the studies' design has been limited. Three examples are discussed, which illustrate the ethical concerns that might result from the failure of clinical researchers to fully inform patients.

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Use of CA-125 in Clinical Trial Evaluation of New Therapeutic Drugs for Ovarian Cancer

Cited by 120 publications

References 79 publications

A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation

A phase II study of docetaxel weekly in combination with carboplatin every three weeks as first line chemotherapy in stage IIB-IV epithelial ovarian cancer: Neurological toxicity and quality-of-life evaluation

A phase Ib study of pertuzumab, a recombinant humanised antibody to HER2, and docetaxel in patients with advanced solid tumours

Informing prospective research subjects of the influence of regulatory requirements for drug approval on the design of clinical trials in oncology

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