OVPSYCH2: A randomized controlled trial of psychological support versus standard of care following chemotherapy for ovarian cancer.

BACKGROUND: Fear of disease progression (FOP) is a rational concern for women with Ovarian Cancer (OC) and depression is also common. To date there have been no randomized trials assessing the impact of psychological intervention on depression and FOP in this patient group. PATIENTS AND METHODS: Patients with primary or recurrent OC who had recently completed chemotherapy were eligible if they scored between 5 and 19 on the PHQ-9 depression and were randomized 1:1 to Intervention (3 standardized CBT-based sessions in the 6-12 weeks post-chemotherapy) or Control (standard of care). PHQ-9, FOP-Q-SF, EORTC QLQ C30 and OV28 questionnaires were then completed every 3 months for up to 2 years. The primary endpoint was change in PHQ-9 at 3 months. Secondary endpoints were change in other scores at 3 months and all scores at later timepoints. RESULTS: 182 patients registered; 107 were randomized; 54 to Intervention and 53 to Control; mean age 59 years; 75 (70%) had completed chemotherapy for primary and 32 (30%) for relapsed OC and 67 patients completed both baseline and 3-month questionnaires. Improvement in PHQ-9 was observed for patients in both study arms at three months compared to baseline but there was no significant difference in change between Intervention and Control. A significant improvement on FOP-Q-SF scores was seen in the Intervention arm, whereas for those in the Control arm FOP-Q-SF scores deteriorated at 3 months (intervention effect = -4.4 (-7.57, -1.22), p-value = 0.008). CONCLUSIONS: CBT-based psychological support provided after chemotherapy did not significantly alter the spontaneously improving trajectory of depression scores at three months but caused a significant improvement in FOP. Our findings call for the routine implementation of FOP support for ovarian cancer patients.

Invasive group A streptococcal infections in North West England: epidemiology, risk factors and fatal infection.

OBJECTIVES: In England, notifications of invasive group A streptococcal (iGAS) infections have increased since 2015. We describe time trends, risk factors, as well as clinical and infection characteristics amongst iGAS cases in North West England, focussing on people who inject drugs (PWIDs), prisoners and homeless populations (referred to as risk groups), and analyse factors for fatal infection. STUDY DESIGN: The study design used was a cross-sectional study. METHODS: Data for all iGAS cases notified to Public Health England North West between January 2016 and May 2019 were used. Analysis consisted of time trend analysis, descriptive statistics, hypothesis testing to investigate differences in clinical and infection characteristics between risk and non-risk groups and binary logistic regression to identify factors associated with fatal infection. RESULTS: There were 1353 cases. Two hundred and two were amongst risk groups, who were predominantly PWIDs in Greater Manchester. Soft tissue risk factors were widespread. There were differences in strain-type between risk and non-risk groups. Female gender, cancer, emm1.0 and emm5.23 were associated with increased odds of death, whilst cellulitis was associated with reduced odds. The relationship between age and death was U-shaped. CONCLUSIONS: iGAS has increased in North West England since 2016, including amongst PWIDs. This may be due to emm-type replacement, barriers to good hygiene and increasing colonisation.

Bowel cancer screening in an English prison: a qualitative service evaluation.

OBJECTIVES: Bowel cancer screening home-testing kits are offered every two years to individuals aged 60-74 years in the United Kingdom (UK), with prisoners eligible for screening in the same way as the general population. There are currently major changes planned to the bowel cancer screening programme in England, with the transition to the single-sample faecal immunochemical test (FIT) and the planned lowering of the age limit from 60 to 50 years. In this project, we aimed to explore processes and beliefs around bowel cancer screening in an English prison. STUDY DESIGN: This is a qualitative study. METHODS: Semistructured qualitative interviews were conducted with eight prisoners and four staff members in a male prison in North West England. Data were analysed via thematic analysis. RESULTS: Promoting and impeding factors to screening were identified. There was high willingness amongst prisoners to be screened for bowel cancer, with screening seen as important and having benefits for the individual and healthcare system. However, there was often low awareness of screening and there were psychological challenges associated with screening. Prison healthcare staff were widely respected and were a motivator to accept screening, with prisoners viewing prison as a good opportunity to access health care. Despite this, prison life was characterised by competing priorities, with security taking precedence, and screening sometimes a low priority for staff and prisoners. There were also considerable logistical challenges to delivering bowel cancer screening in a prison, and the system was not comparable with that in the community. Providing good-quality understandable information, though challenging, was key. CONCLUSIONS: This is the first project to explore entering the bowel cancer screening programme in UK prisons, and promoting and impeding factors to the take-up of screening have been identified. This information could be practically used by local commissioners and policymakers to aid the design of staff and prisoner interventions to maximise uptake of bowel cancer screening in prisons. As the planned changes to bowel cancer screening in England are likely to increase the number of eligible prisoners, this work could also be used to inform any service reconfiguration required to accommodate these changes.

Did school characteristics affect the uptake of meningococcal quadrivalent vaccine in Greater Manchester, United Kingdom?

OBJECTIVES: The objective of this study was to assess if school characteristics were associated with the uptake of the meningococcal ACWY (MenACWY) vaccine in Greater Manchester in 2017/18. STUDY DESIGN: This is an ecological cross-sectional study. METHODS: We analysed data on all 129 schools in seven local authorities in Greater Manchester from the Department for Education and from local child health information systems to determine whether school characteristics, including school type and Ofsted effectiveness score, were associated with vaccine uptake. Schools with no eligible pupils were excluded. We undertook single-variable and multivariable analysis and considered key interactions. RESULTS: The overall uptake rate was 80.7%, with a median uptake per school of 80.6% (interquartile range, 69.0%-87.4%). Lower vaccination rates were associated with lower overall effectiveness scores (odds ratio [OR]: 3.54, 95% confidence interval [CI]: 3.00-4.19) and lower numbers of pupils eligible for vaccination (OR: 1.39, 95% CI: 1.28-1.51). Schools with a lower percentage of pupils for whom English is a second language and high deprivation were associated with lower uptake (OR: 1.58, 95% CI: 1.41-1.78). In addition, community schools (the schools with the most local authority oversight) had lower vaccination rates than other categories of schools. CONCLUSIONS: In this study, uptake rates of the MenACWY vaccine were associated with all five school characteristics considered. Effectiveness scores for schools had the largest association with vaccine uptake, with poorer schools having lower uptake. These characteristics should be used by vaccination providers to prioritise their interventions to increase immunisation rates.

Combining conventional therapy with immunotherapy: A risky business?

Because of the failure of immunotherapy as single agent in a number of cancers, current clinical trials are focusing on combining immunotherapy with other therapies. The most frequently chosen combination for immunotherapy is chemotherapy. However, almost no preclinical data on this combination is available. Some studies even showed a dismal effect of combining chemotherapy with immunotherapy. Taken into account that each of the therapies chosen in a combination will influence the cancer cells but also immune effector cells as well as immunosuppressive cells, and that these three partners will also interact with each other, launching a combination to the patient without proper immune monitoring and preclinical evidence might be devastating.

A phase I, pharmacokinetic and pharmacodynamic study of GSK2256098, a focal adhesion kinase inhibitor, in patients with advanced solid tumors.

BACKGROUND: Focal adhesion kinase (FAK) is important in cancer growth, survival, invasion, and migration. The purpose of this study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the FAK inhibitor, GSK2256098, in cancer patients. PATIENTS AND METHODS: The dose of GSK2256098 was escalated, in cohorts of patients with advanced cancer, from 80 to 1500 mg, oral twice daily (BID), until the MTD was determined. Serial blood samples were obtained from all patients, and the PK was determined. Paired tumor biopsies were obtained in select patients, and the level of phospho-FAK (pFAK) was determined. RESULTS: Sixty-two patients (39 males, 23 females; median age 61 y.o., range 21-84) received GSK2256098. Dose-limiting toxicities of grade 2 proteinuria (1000 mg BID), grade 2 fatigue, nausea, vomiting (1250 mg BID), and grade 3 asthenia and grade 2 fatigue (1500 mg BID) were reported with the MTD identified as 1000 mg BID. The most frequent adverse events (AEs) were nausea (76%), diarrhea (65%), vomiting (58%), and decreased appetite (47%) with the majority of AEs being grades 1-2. The PK was generally dose proportional with a geometric mean elimination half-life range of 4-9 h. At the 750, 1000, and 1500 mg BID dose levels evaluated, the pFAK, Y397 autophosphorylation site, was reduced by ∼80% from baseline. Minor responses were observed in a patient with melanoma (-26%) and three patients with mesothelioma (-13%, -15%, and -17%). In the 29 patients with recurrent mesothelioma, the median progression-free survival was 12 weeks with 95% CI 9.1, 23.4 weeks (23.4 weeks merlin negative, n = 14; 11.4 weeks merlin positive, n = 9; 10.9 weeks merlin status unknown, n = 6). CONCLUSIONS: GSK2256098 has an acceptable safety profile, has evidence of target engagement at doses at or below the MTD, and has clinical activity in patients with mesothelioma, particularly those with merlin loss.

Radiological predictors of cytoreductive outcomes in patients with advanced ovarian cancer.

OBJECTIVE: To assess site of disease on preoperative computed tomography (CT) to predict surgical debulking in patients with ovarian cancer. DESIGN: Two-phase retrospective cohort study. SETTING: West London Gynaecological Cancer Centre, UK. POPULATION: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal cancer undergoing cytoreductive surgery. METHODS: Preoperative CT images were reviewed by experienced radiologists to assess the presence or absence of disease at predetermined sites. Multivariable stepwise logistic regression models determined sites of disease which were significantly associated with surgical outcomes in the test (n = 111) and validation (n = 70) sets. MAIN OUTCOME MEASURES: Sensitivity and specificity of CT in predicting surgical outcome. RESULTS: Stepwise logistic regression identified that the presence of lung metastasis, pleural effusion, deposits on the large-bowel mesentery and small-bowel mesentery, and infrarenal para-aortic nodes were associated with debulking status. Logistic regression determined a surgical predictive score which was able to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846) and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of 75.0% and negative predictive value of 65.2%. These results remained significant in a recent validation set. There was a significant difference in residual disease volume in the test and validation sets (P < 0.001) in keeping with improved optimal debulking rates. CONCLUSIONS: The presence of disease at some sites on preoperative CT scan is significantly associated with suboptimal debulking and may be an indication for a change in surgical planning.

LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.

Sexual activity and functioning in ovarian cancer survivors: an internet-based evaluation.

OBJECTIVES: Sexual dysfunction is a known complication of treatment for many cancers, but there have been relatively few studies investigating outcomes for ovarian cancer survivors. We have previously reported that women treated for ovarian cancer experience persistent psychological and physical problems. Sexual functioning was highlighted as a significant factor and we sought to investigate this further. METHODS: Women were invited to complete a questionnaire using both paper and online response formats. A validated tool, the Sexual Activity Questionnaire, was used to obtain information from women following a diagnosis of ovarian cancer. RESULTS: Across all responders (n = 102, mean age 51.3 years), 63% of women reported their ovarian cancer diagnosis had negatively changed their sex life. The most common reasons given for an absence of sexual activity were a lack of interest in sex, physical problems that prevented sex or no partner. Of the 46% of responders who stated they were sexually active, 77% reported pain or discomfort during intercourse and 87% described vaginal dryness. CONCLUSION: For the majority of women, treatment for ovarian cancer negatively impacts on their sex lives. Many of the symptoms described by participants are potentially reversible and clinicians should be open to raising the issue of sexual functioning with their patients.

Weekly AUC2 carboplatin in acquired platinum-resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase III OVATURE multicenter randomized study.

BACKGROUND: Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients. PATIENTS AND METHODS: A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life. RESULTS: The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (CI) 11.1-21.0] versus 20.1 weeks for group 2 (95% CI = 13.1-33.4); P = 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% CI 32.0-45.3) versus 45.7 weeks (95% CI 35.6-58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity. CONCLUSIONS: Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies.

Safety, cost-effectiveness and feasibility of daycase paracentesis in the management of malignant ascites with a focus on ovarian cancer.

BACKGROUND: Paracentesis for malignant ascites is usually performed as an in-patient procedure, with a median length of stay (LoS) of 3-5 days, with intermittent clamping of the drain due to a perceived risk of hypotension. In this study, we assessed the safety of free drainage and the feasibility and cost-effectiveness of daycase paracentesis. METHOD: Ovarian cancer admissions at Hammersmith Hospital between July and October 2009 were audited (Stage 1). A total of 21 patients (Stage 2) subsequently underwent paracentesis with free drainage of ascites without intermittent clamping (October 2010-January 2011). Finally, 13 patients (19 paracenteses, Stage 3), were drained as a daycase (May-December 2011). RESULTS: Of 67 patients (Stage 1), 22% of admissions and 18% of bed-days were for paracentesis, with a median LoS of 4 days. In all, 81% of patients (Stage 2) drained completely without hypotension. Of four patients with hypotension, none was tachycardic or symptomatic. Daycase paracentesis achieved complete ascites drainage without complications, or the need for in-patient admission in 94.7% of cases (Stage 3), and cost £954 compared with £1473 for in-patient drainage. CONCLUSIONS: Free drainage of malignant ascites is safe. Daycase paracentesis is feasible, cost-effective and reduces hospital admissions, and potentially represents the standard of care for patients with malignant ascites.

Extended weekly dose-dense paclitaxel/carboplatin is feasible and active in heavily pre-treated platinum-resistant recurrent ovarian cancer.

There is increasing evidence of the efficacy of dose-dense therapy in the management of platinum-resistant/refractory ovarian cancer. We report our experience of extended weekly carboplatin and paclitaxel in this population group. Twenty patients with platinum-resistant/refractory ovarian cancer received carboplatin AUC 3 and paclitaxel 70 mg m(-2) on day 1, 8, 15 q 4 weekly for six planned cycles. Toxicity was assessed using Common Toxicity Criteria. Response was evaluated using radiological and CA125 criteria. Median age was 61 years (range 40-74 years). Median number of prior therapies is three (range 1-8). Response rate was 60% by radiological criteria (RECIST) and 76% by CA125 assessment. Grade 3 toxicities consisted of neutropenia (29% of patients) and anaemia (5%). One patient experienced grade 4 neutropenia. No grade 3/4 thombocytopaenia was reported. Fatigue, nausea and peripheral neuropathy were the most frequent non-hematological side effects. Median progression-free survival was 7.9 months and overall survival was 13.3 months. The dynamics of response to dose-dense therapy were as rapid as with front-line therapy within the same patient. This dose-dense regimen can be extended to at least 18 weekly cycles over 6 months and is well tolerated with high response rates in heavily pre-treated, platinum-resistant ovarian cancer. It forms a highly active and tolerable cytotoxic scaffold to which molecular-targeted therapies can be added in platinum-resistant ovarian cancer.

A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel in patients with advanced solid tumours.

The aim of this study is to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PKs) and efficacy of ispinesib (SB-715992) in combination with docetaxel. Patients with advanced solid tumours were treated with ispinesib (6-12 mg m(-2)) and docetaxel (50-75 mg m(-2)). Docetaxel was administered over 1 h followed by a 1-h infusion of ispinesib on day 1 of a 21-day schedule. At least three patients were treated at each dose level. Blood samples were collected during cycle 1 for PK analysis. Clinical response assessments were performed every two cycles using RECIST guidelines. Twenty-four patients were treated at four dose levels. Prolonged neutropaenia and febrile neutropaenia were dose limiting in six and two patients, respectively. The MTD was ispinesib 10 mg m(-2) with docetaxel 60 mg m(-2). Pharmacokinetic assessment demonstrated concentrations of ispinesib and docetaxel, consistent with published data from single agent studies of the drugs. Seven patients (six hormone refractory prostate cancer (HRPC), one renal cancer) had a best response of stable disease (>or=18 weeks). One patient with HRPC had a confirmed >50% prostatic-specific antigen decrease. The MTD for ispinesib and docetaxel was defined and the combination demonstrated an acceptable toxicity profile. Preliminary PK data suggest no interaction between ispinesib and docetaxel.

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

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(-2)) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m(-2)) 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(-2) 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(-2) 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 >50% 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(-2) and 420 mg pertuzumab following a loading dose of 840 mg.

A phase I study of intravenous TZT-1027 administered on day 1 and day 8 of a three-weekly cycle in combination with carboplatin given on day 1 alone in patients with advanced solid tumours.

BACKGROUND: TZT-1027 is a tubulin-binding drug and synthetic derivative of dolastatin-10 with cytotoxic and antivascular activity in vitro and in vivo. Studies have demonstrated anti-tumour activity in several tumour types. METHODS: Patients were treated with escalating doses of TZT-1027 and carboplatin at doses from 1.6 to 2.0 mg/m2 and AUC 4 and 5 respectively. For pharmacokinetic analysis, plasma sampling was done during the first course using a high-performance liquid chromatographic assay. RESULTS: 14 patients received a total of 55 cycles at three dose levels. Dose limiting toxicities (DLTs) were first observed with 1.6 mg/m2 TZT-1027 and carboplatin AUC 5; 1 patient had grade 4 neutropenia and a delay in day 8 treatment occurred in two patients (gr 2 fatigue, gr 3 diarrhoea). At TZT-1027 2 mg/m2 and carboplatin AUC 5, one patient experienced grade 3 paralytic ileus. The most frequent toxicities were neutropenia, anaemia, fatigue, constipation, infection and vomiting. Peripheral neuropathy was reported in 36% of patients. One patient (pancreatic adenocarcinoma) achieved a partial response lasting 181 days. Pharmacokinetic analysis did not demonstrate any interaction between TZT-1027 and carboplatin. CONCLUSIONS: The recommended phase II dose is TZT-1027 1.6 mg/m2 and carboplatin AUC 5. No evidence of a PK interaction between these agents was observed.

Drugging cell cycle kinases in cancer therapy.

Cell cycle kinases are comprised of cyclin-dependent kinases (Cdks), non-Cdk kinases such as Plk-1 and Aurora and checkpoint proteins such as Chk1 and Chk2. Though ubiquitous to dividing cells, many cell cycle kinases are amplified or over-expressed in malignancy and are potential targets for anti-cancer therapies. Cdk inhibiting drugs (such as flavopiridol, UCN-01, E7070, R-Roscovitine and BMS-387032) have shown preclinical and clinical anticancer activity. However, many of these agents are promiscuous and undiscerning, targeting other non-cell cycle kinases and affecting normal cells, thereby causing significant toxicity. To overcome this, a new generation of Cdk inhibitors are in development with greater target specificity, as well as others that inhibit non-Cdk cell cycle kinases, both directly and indirectly. The outcome of early clinical trials involving these agents is awaited, but these certainly represent a promising new area of anticancer drug development.

Performance status score: do patients and their oncologists agree?

Oncologists traditionally assess their patients' ECOG performance status (PS), and few studies have evaluated the accuracy of these assessments. In this study, 101 patients attending a rapid access clinic at Papworth Hospital with a diagnosis of lung cancer were asked to assess their own ECOG PS score on a scale between 0 and 4. Patients' scores were compared to the PS assessment of them made by their oncologists. Of 98 patients with primary non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), weighted kappa statistics showed PS score agreement between patient and oncologist of 0.45. Both patient- and oncologist-assessed scores reflected survival duration (in NSCLC and SCLC) as well as disease stage (in NSCLC), with oncologist-assessed scores being only marginally more predictive of survival. There was no sex difference in patient assessment of PS scores, but oncologists scored female patients more pessimistically than males. This study showed that, with few exceptions, patients and oncologists assessed PS scores similarly. Although oncologists should continue to score PS objectively, it may benefit their clinical practice to involve their patients in these assessments.

Phase II study to evaluate combining gemcitabine with flutamide in advanced pancreatic cancer patients.

A phase II study was undertaken to determine the safety of combining flutamide with gemcitabine, with response rate being the primary end point. Twenty-seven patients with histologically proven, previously untreated, unresectable pancreatic adenocarcinoma received gemcitabine, 1 g m(-2) intravenously on days 1, 8 and 15 of a 28 day cycle, and flutamide 250 mg given orally three times daily. Treatment was halted if there was unacceptable toxicity, or evidence of disease progression. Toxicity was documented every cycle. Tumour assessment was undertaken after cycles 2 and 4, and thereafter at least every additional four cycles. One hundred and seventeen cycles of treatment were administered, median four cycles per patient (range 1-18). Gemcitabine combined with flutamide was well tolerated, with most toxicities being recorded as grade 1 or 2 and only nine treatment cycles associated with grade 3 toxicity. The most frequent toxicity was myelosuppression. One case of transient jaundice was recorded. The commonest symptomatic toxicity was nausea and vomiting. The response rate was 15% (four partial responses), median survival 6 months and 22% of patients were alive at 1 year. These results suggest antitumour activity of the combination therapy to be equivalent to single agent gemcitabine.

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours.

Little literature exists on the safety of early pregnancy following chemotherapy. Here we assess the rate of relapse and foetal outcome in women who have completed single and multi-agent chemotherapy for gestational trophoblastic tumours. The records of 1532 patients treated for persistent gestational trophoblastic tumours at Charing Cross Hospital between 1969 and 1998 were reviewed. Patients were defined as receiving single agent or multi-agent treatment. Relapse rates and foetal outcome were reviewed in the 230 patients who became pregnant within 12 months of completing chemotherapy. In the single agent group 153 (22%) of 691 patients conceived early. Three subsequently relapsed. In the multi-agent group, 77 (10%) of 779 patients conceived early, two then relapsed. Relapse rates were 2% (3 out of 153) and 2.5% (2 out of 77) for each group compared to 5% and 5.6% in the comparative non-pregnant groups. Outcomes of 230 early pregnancies: 164 (71%) delivered at full term, 35 (15%) terminations, 26 (11%) spontaneous abortions, three (1.3%) new hydatidiform moles and two (1%) stillbirths. Early pregnancies were more common in the single agent group (P<0.001), but spontaneous miscarriages and terminations were more likely to occur in the multi-agent group (P=0.04 and 0.03, respectively). Of the full-term pregnancies, three (1.8%) babies were born with congenital abnormalities. Patients in either group who conceive within 12 months of completing chemotherapy are not at increased risk of relapse. Though, we still advise avoiding pregnancy within 12 months of completing chemotherapy, those that do conceive can be reassured of a likely favourable outcome. DOI: 10.1038/sj/bjc/6600041 www.bjcancer.comCopyright 2002 The Cancer Research Campaign