A phase II study of carboplatin AUC-10 guided by positron emission tomography-defined metabolic response in metastatic seminoma.

Introduction: Carboplatin monotherapy for metastatic seminoma at a dose of AUC-10 has shown promising activity. Three or four cycles have been given with most haematological side-effects seen with the 4th cycle. An early response might allow de-escalation of therapy.

Phase I study of nintedanib incorporating dynamic contrast-enhanced magnetic resonance imaging in patients with advanced solid tumors.

Background: This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors.

Methods: Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.

Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer.

Objective: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis.

Current controversies in the management of germ cell ovarian tumours.

Purpose Of Review: Fewer than 70 new cases of malignant ovarian germ cell tumours (MOGCTs) are seen each year in the UK. Because of their rarity, no randomized trials have been reported and many of the advances in management have arisen from adopting practices developed for managing male germ cell tumours (GCTs). Not surprisingly, there have been few important publications related to ovarian germ cell tumuors over the past 2 years.

Pathological findings after primary chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection for advanced germ cell tumours.

Objective: To determine the differential response to systemic chemotherapy in patients undergoing simultaneous orchidectomy and retroperitoneal lymph node dissection (RPLND) after chemotherapy for metastatic testicular cancer.

Patients And Methods: Patients who underwent simultaneous RPLND and orchidectomy after chemotherapy were identified from our clinical databases. Postoperative pathological findings and patient characteristics were reviewed.

Phase I trial of combretastatin A4 phosphate (CA4P) in combination with bevacizumab in patients with advanced cancer.

Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.

Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m(2) on day 1, day 8, and then every 14 days.

Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors.

Purpose: Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents.

Experimental Design: Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors.

Results: Doses were escalated in single-patient cohorts from 0.

Biologicals in the upfront treatment of ovarian cancer: focus on bevacizumab and poly (adp-ribose) polymerase inhibitors.

Biologicals have made a major impact in the management of several cancers, but have hitherto had a negligible impact in ovarian cancer. Fortunately, ovarian cancer has been much more sensitive to cytotoxic chemotherapy than many cancers, so treatments were still available. However, improvements are required as more than 80% of patients who present with advanced ovarian cancer eventually will die as a result of their disease.

Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).

Purpose: Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported.

Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG).

The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the serum marker CA 125 and has specified the situations where these criteria should be used. However, the publications did not include detailed definitions, nor were they written to accommodate the new version of Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) now available.

What surveillance plan should be advised for patients in remission after completion of first-line therapy for advanced ovarian cancer?

Based on the results of the Medical Research Council OVO5/European Organisation for Research and Treatment of Cancer 55955 trial, the follow-up plan I recommend for patients in remission after completion of first-line therapy for advanced ovarian cancer is appointments: every 3 months for 2 years, every 4 months on the third year, then every 6 months thereafter, and discharge if no relapse by 10 years. History and examination (not internal) should be performed at each appointment. CA-125 should only be measured if there is a suspicion of relapse or at patient's request.

Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial.

Background: Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer. In the MRC OV05/EORTC 55955 collaborative trial, we aimed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence.

Methods: Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this randomised controlled trial.

Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.

Background: The potential of gemcitabine to interact with carboplatin was explored in a phase II trial in platinum-resistant ovarian cancer. Peripheral blood lymphocytes were sampled after drug administration to measure DNA interstrand cross-link formation and repair.

Patients And Methods: Forty patients received carboplatin target area under concentration-time curve (AUC 4) followed by gemcitabine 1,000 mg/m(2) with a second dose of gemcitabine on day 8.

How to follow-up patients with epithelial ovarian cancer.

Purpose Of Review: Despite optimal primary treatment most patients with advanced epithelial ovarian cancer will relapse. This review discusses the controversy regarding surveillance and the timing of treatment for recurrent disease.

Recent Findings: Routine physical examination has a limited role in the detection of recurrent ovarian cancer.

First-line therapy for ovarian cancer with carboplatin followed by paclitaxel-gemcitabine (SCOTROC5): a feasibility study and comparative analysis of the SCOTROC series.

Background: We have conducted a series of four feasibility studies in stage Ic-IV ovarian cancer exploring six sequential first-line schedules with the same entry criteria in a total of 339 patients. Here we present the results of the sixth study, and an analysis of the overall series.

Methods: In this trial patients received 4 cycles of carboplatin AUC 7 every 3 weeks, followed by 4 cycles of concurrent paclitaxel 175 mg/m(2) (day 1) and gemcitabine 1000 mg/m(2) (days 1 and 8) every 3 weeks.

A phase I trial of radioimmunotherapy with 131I-A5B7 anti-CEA antibody in combination with combretastatin-A4-phosphate in advanced gastrointestinal carcinomas.

Purpose: In preclinical models, radioimmunotherapy with (131)I-A5B7 anti-carcinoembryonic antigen (CEA) antibody ((131)I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas.

Experimental Design: Patients had CEA of 10 to 1,000 microg/L, QTc < or =450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry.

Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations.

On May 3, 2008, a National Cancer Institute (NCI)-sponsored open consensus conference was held in Toronto, Ontario, Canada, during the 2008 International Society for Magnetic Resonance in Medicine Meeting. Approximately 100 experts and stakeholders summarized the current understanding of diffusion-weighted magnetic resonance imaging (DW-MRI) and reached consensus on the use of DW-MRI as a cancer imaging biomarker. DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators.

Clinical trial endpoints in ovarian cancer: report of an FDA/ASCO/AACR Public Workshop.

Objective: The unique characteristics of cancer, particularly issues involving the use of surrogate endpoints in clinical trials, present special challenges in the development of cancer drugs. In response, the U.S.

Management of asymptomatic patients on follow-up for ovarian cancer with rising CA-125 concentrations.

In most women who have been treated for ovarian cancer, serum concentrations of the tumour marker cancer antigen (CA)-125 will serially rise on average 4 months before they develop symptoms or signs of relapse. Whether or not early reintroduction of treatment produces a survival advantage is unclear. Although a high chance exists that tumour response can be achieved with chemotherapy, complete cure of these patients is rarely possible.

18fluorodeoxyglucose positron emission tomography in the prediction of relapse in patients with high-risk, clinical stage I nonseminomatous germ cell tumors: preliminary report of MRC Trial TE22--the NCRI Testis Tumour Clinical Study Group.

Purpose: There are several management options for patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT); this study examined whether an 18fluorodeoxyglucose positron emission tomography (18FDG PET) scan could identify patients without occult metastatic disease for whom surveillance is an attractive option.

Methods: High-risk (lymphovascular invasion positive) patients with CS1 NSGCT underwent 18FDG PET scanning within 8 weeks of orchidectomy or marker normalization. PET-positive patients went off study; PET-negative patients were observed on a surveillance program.

Randomized trial of two or five computed tomography scans in the surveillance of patients with stage I nonseminomatous germ cell tumors of the testis: Medical Research Council Trial TE08, ISRCTN56475197--the National Cancer Research Institute Testis Cancer Clinical Studies Group.

Purpose: Surveillance is a standard management approach for stage I nonseminomatous germ cell tumors (NSGCT). A randomized trial of two versus five computed tomography (CT) scans was performed to determine whether the number of scans influenced the proportion of patients relapsing with intermediate- or poor-prognosis disease at relapse.

Methods: Patients with clinical stage I NSGCT opting for surveillance were randomly assigned to chest and abdominal CT scans at either 3 and 12 or 3, 6, 9, 12, and 24 months, with all other investigations identical in the two arms.

Dynamic MRI for imaging tumor microvasculature: comparison of susceptibility and relaxivity techniques in pelvic tumors.

Purpose: To assess the reproducibility of intrinsic relaxivity and both relaxivity- and susceptibility-based dynamic contrast enhanced (DCE) MRI in pelvic tumors; to correlate kinetic parameters obtained and to assess whether acute antivascular effects are seen in response to cisplatin- or taxane-based chemotherapy.

Materials And Methods: T1-weighted and T2*-weighted DCE-MRI and basal R2* measurements were performed on three consecutive days in women with gynecological tumors. The third scan was 21.

Malignant ovarian germ cell tumors: identification of novel prognostic markers and long-term outcome after multimodality treatment.

Purpose: Malignant ovarian germ cell tumors are rare and knowledge about prognostic parameters currently is limited. This study was undertaken to evaluate long-term outcome of patients with malignant ovarian germ cell tumors (MOGCTs) after chemotherapy and to assess prognostic parameters.

Patients And Methods: A total of 113 patients with stage IC to IV MOGCTs were included into this retrospective study.

Controversies in the management of germ cell tumours of the ovary.

Purpose Of Review: Ovarian germ cell tumours are rare, but curable at all stages of disease. This review gives an outline of the main controversies regarding the management of this disease.

Recent Findings: Pelvic malignancies are very rare during pregnancy, which should avoid the need for radical surgery or termination in these patients.