R. Gunapala

A phase II study of 18F-fluorodeoxyglucose PET–CT in non-small cell lung cancer patients receiving erlotinib (Tarceva®); objective and symptomatic responses at 6 and 12 weeks

BACKGROUND The aim of this study was to assess if (18)F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)-CT scanning could minimise the time non-responding patients were exposed to erlotinib (Tarceva). METHODS Patients were selected for clinical factors that would predict response to erlotinib. A FDG PET-CT and diagnostic contrast-enhanced (traditional) CT scan were carried out at baseline, and then a FDG PET-CT at 6 weeks and a traditional CT at 12 weeks were repeated. The primary end-point was rate of early progression in patients after 6 weeks, of which a minimum 12 out of 35 were required to make the study worthwhile. The responses at 6 (PET-CT) and 12 weeks (traditional CT) were compared and correlated with symptomatic response at both these time points. RESULTS Forty seven patients were recruited with 38 and 33 patients assessable by FDG PET-CT at 6 weeks and traditional CT at 12weeks, respectively. There was good correlation between Partial response (PR) at both time points and all 10 patients who had a PR at 12 weeks had a PR at 6 weeks. Of the 13 patients with progressive disease (PD) at 12 weeks, seven had PD at 6 weeks and could have had their treatment stopped early. No evaluable patient with stable disease (SD) (8/38) or PD (9/38) on FDG PET-CT at 6 weeks went on to have a later response. Symptomatic response at 6 or 12 weeks did not correlate well with objective response on scanning at either time point. CONCLUSIONS The primary end-point of this study was met as >12 (15/38) patients could have stopped treatment early on the basis of the FDG PET-CT scan result. A FDG PET-CT evaluable response of SD or PD at 6 weeks does predict future lack of response. No correlation was found between response and symptomatic response at either 6 or 12 weeks.

Diethylstilbestrol in castration‐resistant prostate cancer

Study Type – Therapy (case series)

Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres

Objectives We conducted a retrospective review of patients with extrapulmonary small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns of relapse and outcomes by primary site. Setting We have reviewed the outcomes of one of the largest data sets of consecutive patients with EPSCC identified from two major cancer centres. Participants Consecutive patients with a histopathological diagnosis of EPSCC from the two institutions were retrospectively identified. Primary and secondary outcome measures Outcomes were evaluated including stage at presentation, treatments given, sites of relapse, time to distant relapse, progression-free survival and overall survival (OS). Results From a total 159 patients, 114 received first-line chemotherapy, 80.5% being platinum-based. Response rate was 48%. Commonest primary sites were genitourinary and gynaecological. 44% of patients presented with metastatic disease. 55.9% relapsed with liver the commonest site, whereas only 2.5% developed brain metastases. Median OS was 13.4 months for all patients, 7.6 months and 19.5 months for those with metastatic and non-metastatic disease, respectively. Gynaecological and head and neck patients had significantly better OS compared to gastrointestinal patients. Conclusions EPSCCs demonstrate high response rates to chemotherapy and high rates of distant metastases. Primary sites may influence prognosis, and survival is optimal with a radical strategy. Brain metastases are rare and we therefore do not recommend prophylactic cranial irradiation.

Patient factors, health care factors and survival from lung cancer according to ethnic group in the south of London, UK

International and UK data suggest that there are ethnic differences in survival for some malignancies. The aim of the present study was to identify any health inequalities related to lung cancer and ethnicity. Data on 423 patients with a diagnosis of lung cancer treated at a large specialist cancer hospital in London UK were analysed. Data on stage of disease at diagnosis, co-morbidities, socio-economic status, treatments received and survival were collected and examined for differences by ethnic group. There was a significant difference between black and minority ethnic (BME) patients and White-European patients in socio-economic status (Chi-square test P-value < 0.001). BME patients were over-represented in the most deprived socio-economic groups and under-represented in the most affluent. There were no significant differences in histology, stage of disease, co-morbidities and performance status or treatments received between the different ethnic groups. Ethnicity was not associated with survival. Significant prognostic factors for overall survival were performance status (P < 0.001), stage of disease (P = 0.001) and gender (P = 0.003). Our findings suggest that patients from BME groups are over-represented in more deprived socio-economic groups; however, this did not impact on significant prognostic factors or the treatments that they received. Importantly ethnicity did not influence survival.

33 Outcomes of patients undergoing adjuvant platinum–vinorelbine chemotherapy for resected non-small cell lung cancer (NSCLC)

Introduction: Cisplatin vinorelbine adjuvant chemotherapy significantly improves survival in resected NSCLC. We evaluated outcomes of patients receiving adjuvant chemotherapy in our institution between 2006 2011. Methods: Outcomes of stage IB IIIA NSCLC patients who received platinum vinorelbine following radical lung surgery were collected and analysed to assess overall survival (OS), progression-free survival (PFS), and treatment intensity. Results: 53 patients were identified (M:F, 23:30), mean age 62, and 35% were adenocarcinoma. Resected stages were IB-IIIA, with 33% staged IIIA. When tested, EGFR mutation prevalence was 33% (39% never smokers; 61% ever smokers). Median chemotherapy cycles given was 4 with no toxicity related deaths. There was no difference in PFS or OS in patients having carboplatin compared with cisplatin. Significantly improved OS in patients that received 3 cycles of chemotherapy was observed (HR = 0.25, 0.07 0.97, p = 0.04). Updated results will be presented at the Annual Meeting. Conclusion: Our small dataset indicates that four cycles of adjuvant platinum vinorelbine chemotherapy is deliverable in the real world setting, and that less than 3 chemotherapy cycles is associated with poorer outcomes.

An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity

Background Vitamin B12 and folic acid (referred to as vitamin supplementation) improves the toxicity profile of pemetrexed containing regimens. Low baseline vitamin B12 and folate levels are reflected in a raised total homocysteine level (HC). Studies have suggested that pretreatment HC levels predict neutropenia toxicity. We have tested supplementation with vitamin B12 and folate in non-pemetrexed platinum-based regimens to decrease treatment-related toxicity and looked for a correlation between toxicity and change in homocysteine levels. Patient and method Eighty-three patients with advanced lung cancer and malignant mesothelioma were randomly assigned to receive platinum-based chemotherapy with (arm A) or without (arm B) vitamin B12 and folic acid supplementation. The primary end point was grade 3/4 neutropenia and death within 30 days of treatment. Secondary end points included quality of life, overall survival (OS) and the relationship between baseline and post supplementation HC levels and toxicity. Results In the intention-to-treat population, no significant difference was seen between the two groups with respect to chemotherapy-induced grade 3/4 neutropenia and death within 30 days of chemotherapy (36% vs 37%; p=0.966, emesis (2% vs 6%; p=0.9) or OS (12.3 months vs 7 months; p=0.41). There was no significant difference in survival rates by baseline HC level (p=0.9). Decrease in HC with vitamin supplementation was less frequent than expected. High baseline HC levels decreased with vitamin supplementation in only 9/36 (25%) patients (successful supplementation). Post hoc analysis showed that patients in arm A who were successfully supplemented (9/36=25%) had less neutropenic toxicity (0% vs 69%; p=0.02) compared to unsupplemented patients. Conclusions The addition of vitamin B12 and folic acid to platinum-containing regimens did not overall improve the toxicity, quality of life or OS. Rates of grade 3/4 neutropenia at 36/37% was as predicted. Further studies to increase the rate of successful supplementation and to further test the biomarker potential of post supplementation HC levels in predicting chemotherapy-induced neutropenia in platinum-based chemotherapy are warranted. Trial registration number: EudracCT 2005-002736-10 ISRCTN8734355.