Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.

We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment. Two partial responses (PR) and 19 stable disease (SD) patients were observed at the 12-week time point. At 28 weeks, according to centrally reviewed Response Evaluation Criteria in Solid Tumours (RECIST) criteria, five PR and 8 SD patients were observed in 50 assessable cases. Overall, objective response rate (5 PR) was of 10%, meeting the pre-specified endpoint. Fourteen patients discontinued due to adverse events. Eleven patients had retinal pigment epithelial detachments which was asymptomatic and reversible in all but one patient. Exploratory ribonucleic acid sequencing (RNA-Seq) analysis was done on patients' samples: 6 differentially-expressed-genes could distinguish those who benefited from the addition of AZD4547.

Impact of the introduction of weekly radiotherapy quality assurance meetings at one UK cancer centre.

OBJECTIVE: The complexity of radiotherapy planning is increasing rapidly. Delivery and planning is subject to detailed quality assurance (QA) checks. The weakest link is often the oncologists' delineation of the clinical target volume (CTV). Weekly departmental meetings for radiotherapy QA (RTQA) were introduced into the Royal Wolverhampton Hospital, Wolverhampton, UK, in October 2011. This article describes the impact of this on patient care. METHODS: CTVs for megavoltage photon radiotherapy courses for all radical, adjuvant and palliative treatments longer than five fractions (with the exception of two field tangential breast treatments not enrolled into clinical trials) were reviewed in the RTQA meeting. Audits were carried out in January 2012 (baseline) and September 2013, each over a 4-week period. Adherence to departmental contouring protocols was assessed and the number of major and minor alterations following peer review were determined. RESULTS: There was no statistically significant difference for major alterations between the two study groups; 8 alterations in 80 patients (10%) for the baseline audit vs 3 alterations from 72 patients (4.2%) in the second audit (p = 0.17). A trend towards a reduction in alterations following peer review was observed. There has, however, been a change in practice resulting in a reduction in variation in CTV definition within our centre and greater adherence to protocols. There is increasing confidence in the quality and constancy of care delivered. CONCLUSION: Introduction of a weekly QA meeting for target volume definition has facilitated consensus and adoption of departmental clinical guidelines within the unit. ADVANCES IN KNOWLEDGE: The weakest areas in radiotherapy are patient selection and definition of the CTV. Engagement in high-quality RTQA is paramount. This article describes the impact of this in one UK cancer centre.

The use of treosulfan and gemcitabine in the treatment of platinum-resistant ovarian cancer.

The combination of treosulfan and gemcitabine (TG) has been shown to have activity in ovarian cancer. These two agents are thought to be synergistic, with gemcitabine causing the persistence of treosulfan-induced DNA crosslinks. This study aimed to investigate the response rates, survival and toxicity in patients with platinum-resistant ovarian cancer treated with TG. A retrospective case note review of the patients treated with TG was performed in one cancer centre between May 1st, 2000 and November 1st, 2005. Estimates of cumulative survival were obtained using the Kaplan-Meier method. Forty-nine patients were identified; median age at diagnosis was 55 years (range, 31-72) and the median follow-up was 45.1 months (range, 12.2-118.3). TG was used as second-, third-, fourth- and fifth-line chemotherapy in 15, 19, 13 and 2 patients, respectively. Fifteen patients (30.6%) had stable disease; 25 (51%), a partial response; 1 (2%), a complete response and 8 (16.3%) had progressive disease. Median survival following diagnosis was 45.1 months and the median relapse-free survival was 12 months. The median survival time from the start of TG was 13.7 months with a relapse-free survival of 6.3 months. The median number of cycles given was 7. The most common toxicity recorded was myelosuppression. There were no treatment-related deaths. TG chemotherapy produced favourable response rates in a heavily pre-treated group of patients with platinum-resistant epithelial ovarian cancer. This doublet warrants further investigation in a phase III trial setting.

Modern chemotherapy management of recurrent ovarian cancer: a multicentre study.

AIMS: The natural history of ovarian cancer has changed over the last 10 years due to more effective drug treatments. The aim of this multicentre audit of the management of recurrent ovarian cancer was to examine the usage of newer drugs in light of the publication of National Institute of Clinical Excellence guidance. MATERIALS AND METHODS: All patients presenting with a first or subsequent relapse of ovarian cancer between August 2001 and February 2003 in nine UK National Health Service centres were identified. Data were recorded retrospectively and prospectively from point of entry into the study and included the modality of primary cancer treatment, the treatment of each subsequent relapse and outcome. RESULTS: In total, 245 evaluable patients were entered on to the database. The mean age was 62 years. All patients received a platinum-based chemotherapy regimen as first-line treatment. One hundred and fifty-five patients (63%) went on to receive third-line chemotherapy and 82 (34%) received fourth-line chemotherapy. The median survival from first relapse was estimated to be in excess of 12 months from our data. The efficacies of the chemotherapy agents used are comparable with the results of published phase III trials. CONCLUSION: This study shows that multicentre audit is feasible and provides useful information on current clinical practice on which to base future research.

Malignant meningitis secondary to ovarian carcinoma: an unusual occurrence.

We report the case history of a patient with Stage IV ovarian carcinoma with leptomeningeal involvement. Although metastasis to other sites is relatively common, this scenario is rare.

Lung cancer after Hodgkin's disease: a nested case-control study of the relation to treatment.

PURPOSE: To investigate the causes of the raised risk of lung cancer in patients who have had Hodgkin's disease, and in particular the relationship to treatment. PATIENTS AND METHODS: A nested case-control study was conducted within a cohort of 5,519 patients with Hodgkin's disease treated in Britain during 1963 through 1993. For 88 cases of lung cancer and 176 matched control subjects, information on treatment and other risk factors was extracted from hospital case-notes, and odds ratios for lung cancer in relation to these factors were calculated. RESULTS: Risk of lung cancer was borderline significantly greater in patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy than those who did not receive this treatment (relative risk [RR] = 1.66; 95% confidence interval [CI], 0.99 to 2.82), and increased with number of cycles of MOPP (P =.07). Exclusion of lung cancers for which histologic confirmation was not available strengthened these associations (RR = 2.41; 95% CI, 1.33 to 4.51; P =.004 for any MOPP and P =.007 for trend with number of cycles of MOPP). Risks were not raised, however, after chlorambucil, vinblastine, procarbazine, and prednisone treatment. There was evidence that the raised risk of lung cancer occurring in relation to radiotherapy was restricted to histologies other than adenocarcinoma. CONCLUSION: The results suggest that MOPP chemotherapy may lead to elevated risk of lung cancer, at least in certain subgroups of patients. The role of chemotherapy in the etiology of lung cancer after Hodgkin's disease deserves further investigation.

Acute mesenteric ischaemia associated with 5-FU, cisplatin and vincristine chemotherapy.

We report a patient with acute superior mesenteric ischaemia following the use of cisplatin, 5-fluorouracil and vincristine combination chemotherapy. From a review of the literature, the possible mechanisms of acute vascular toxicity following chemotherapy are discussed.