Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

Phase I trial of the MEK inhibitor selumetinib in combination with thoracic radiotherapy in non-small cell lung cancer.

BACKGROUND: The RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating treatment response. Selumetinib inhibits MEK and enhances effects of radiotherapy in preclinical studies. PATIENTS AND METHODS: Single-arm, single-centre, open-label phase I trial. Patients with stage III NSCLC unsuitable for concurrent chemo-radiotherapy, or stage IV with dominant thoracic symptoms, were recruited to a dose-finding stage (Fibonacci 3 + 3 design; maximum number = 18) then an expanded cohort (n = 15). Oral selumetinib was administered twice daily (starting dose 50 mg) commencing 7 days prior to thoracic radiotherapy, then with radiotherapy (6-6.5 weeks; 60-66 Gy/30-33 fractions). The primary objective was to determine the recommended phase II dose (RP2D) of selumetinib in combination with thoracic radiotherapy. RESULTS: 21 patients were enrolled (06/2010-02/2015). Median age: 62y (range 50-73). M:F ratio 12(57%):9(43%). ECOG PS 0:1, 7(33%):14(67%). Stage III 16(76%); IV 5(24%). Median GTV 64 cm3 (range 1-224 cm3). 15 patients comprised the expanded cohort at starting dose. All 21 patients completed thoracic radiotherapy as planned and received induction chemotherapy. 13 (62%) patients received the full dose of selumetinib.In the starting cohort no enhanced radiotherapy-related toxicity was seen. Two patients had dose-limiting toxicity (1x grade 3 diarrhoea/fatigue and 1x pulmonary embolism). Commonest grade 3-4 adverse events: lymphopaenia (19/21 patients) and hypertension (7/21 patients). One patient developed grade 3 oesophagitis. No patients developed grade ≥3 radiation pneumonitis. Two patients were alive at the time of analysis (24 and 26 months follow-up, respectively). Main cause of first disease progression: distant metastases ± locoregional progression (12/21 [57.1%] patients). Six patients had confirmed/suspected pneumocystis jiroveci pneumonia. CONCLUSION: We report poor outcome and severe lymphopenia in most patients treated with thoracic radiotherapy and selumetinib at RP2D in combination, contributing to confirmed/clinically suspected pneumocystis jiroveci pneumonia. These results suggest that this combination should not be pursued in a phase II trial.ClinicalTrials.gov reference: NCT01146756.

Barcelona Clinic Liver Cancer and Hong Kong Liver Cancer staging systems for prediction of survival among Hepatocellular Carcinoma patients.

INTRODUCTION: We aimed to compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) staging systems. MATERIALS AND METHODS: This is a retrospective study on patients with newly diagnosed hepatocellular carcinoma (HCC) at the University Malaya Medical Centre between 2011 and 2014. Survival times were analysed using the Kaplan- Meier procedure and comparison between groups was done using the log rank test. RESULTS: The data of 190 patients was analysed. Chronic hepatitis B was the most common aetiology for HCC (43.7%), but a large proportion was cryptogenic or non-alcoholic steatohepatitis-related (41.6%). Only 11.1% were diagnosed early (BCLC Stage 0-A) while majority were diagnosed at an intermediate stage (BCLC Stage B, 53.7%). The median survival rate was significantly different between the different groups when either of the staging systems was used (p<0.05 for all comparisons). However, the two staging systems lacked agreement (weighted kappa 0.519, 95%CI: 0.449, 0.589) with significant difference in median survival rates between BCLC Stage A and HKLC Stage 2, and between BCLC Stage C and HKLC Stage 4. CONCLUSION: Both staging systems were able to stratify patients according to survival, but they only had moderate agreement with significant differences observed in two groups of the staging systems.

An epithelial marker promoter induction screen identifies histone deacetylase inhibitors to restore epithelial differentiation and abolishes anchorage independence growth in cancers.

Epithelial-mesenchymal transition (EMT), a crucial mechanism in development, mediates aggressiveness during carcinoma progression and therapeutic refractoriness. The reversibility of EMT makes it an attractive strategy in designing novel therapeutic approaches. Therefore, drug discovery pipelines for EMT reversal are in need to discover emerging classes of compounds. Here, we outline a pre-clinical drug screening platform for EMT reversal that consists of three phases of drug discovery and validation. From the Phase 1 epithelial marker promoter induction (EpI) screen on a library consisting of compounds being approved by Food and Drug Administration (FDA), Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is identified to exert EMT reversal effects by restoring the expression of an epithelial marker, E-cadherin. An expanded screen on 41 HDACi further identifies 28 compounds, such as class I-specific HDACi Mocetinosat, Entinostat and CI994, to restore E-cadherin and ErbB3 expressions in ovarian, pancreatic and bladder carcinoma cells. Mocetinostat is the most potent HDACi to restore epithelial differentiation with the lowest concentration required for 50% induction of epithelial promoter activity (EpIC-50).The HDACi exerts paradoxical effects on EMT transcriptional factors such as SNAI and ZEB family and the effects are context-dependent in epithelial- and mesenchymal-like cells. In vitro functional studies further show that HDACi induced significant increase in anoikis and decrease in spheroid formation in ovarian and bladder carcinoma cells with mesenchymal features. This study demonstrates a robust drug screening pipeline for the discovery of compounds capable of restoring epithelial differentiation that lead to significant functional lethality.

Enteropathy-associated T-cell lymphoma: An extremely rare cause of chronic diarrhoea.

Chronic diarrhoea in tropical countries may be due to a myriad of causes from infective to non-infective. This case report illustrates the challenges faced in the investigation of a middle-age Chinese gentleman who presented with chronic diarrhoea and weight loss. The diagnosis of type II enteropathy-associated T-cell lymphoma (EATL) was finally made. The diagnosis of EATL was least suspected as the condition is almost unheard of in this part of the world. The epidemiology, presentation, diagnosis, management and prognosis of this rare condition are discussed.

An experience with video-assisted anal fistula treatment (VAAFT) with new insights into the treatment of anal fistulae.

BACKGROUND: The aim of this retrospective study was to assess our experience of 41 patients with anal fistulae treated with video-assisted anal fistula treatment (VAAFT). METHODS: Forty-one consecutive patients with cryptoglandular anal fistulae were included. Patients with low intersphincteric anal fistulae or those with gross perineal abscess were excluded. Eleven (27 %) patients had undergone prior fistula surgery with 5 (12 %) having had three or more previous operations. RESULTS: All patients underwent the diagnostic phase as well as diathermy and curettage of the fistula tracts during VAAFT. Primary healing rate was 70.7 % at a median follow-up of 34 months. Twelve patients recurred or did not heal and underwent a repeat VAAFT procedure utilising various methods of dealing with the internal opening. There was a secondary healing rate of 83 % with two recurrences. Overall, stapling of the internal opening had a 22 % recurrence rate, while anorectal advancement flap had a 75 % failure rate. There was no recurrence seen in six cases after using the over-the-scope-clip (OTSC(®)) system to secure the internal opening. CONCLUSIONS: VAAFT is useful in the identification of fistula tracts and enables closure of the internal opening. Adequate closure is essential with the method used to close large or fibrotic internal openings being the determining factor for success or failure. The OTSC system delivered the most consistent result without leaving a substantial perianal wound. Ensuring thorough curettage and drainage of the tract during VAAFT is also important to facilitate healing. We believe that this understanding will bring about a decrease in the high recurrence rates currently seen in many series of anal fistulae.

A national common massive transfusion protocol (MTP) is a feasible and advantageous option for centralized blood services and hospitals.

BACKGROUND: A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals. METHODS: Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients. RESULTS: There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation. CONCLUSION: This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.

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.

Biomass derived furfural-based facile synthesis of protected (2S)-phenyl-3-piperidone, a common intermediate for many drugs.

An efficient synthetic route towards tosyl-protected (2S)-phenyl-3-piperidone, a common intermediate for many drugs, has been developed in 5 steps in 54% yield from biomass derived furfural. The synthetic utility of the piperidone core structure was demonstrated with the synthesis of a NK1 receptor antagonist.

Gap acceptance of violators at signalised pedestrian crossings.

Gap acceptance of violating pedestrians was studied at seven stretches of signalised pedestrian crossings in Singapore. The provision of the traffic light signals provide a 'safer' crossing option to these pedestrians, as compared to uncontrolled crossings and mid-block arterial roads. However, there are still people choosing to cross at the riskier period (Red Man phase). The paper discusses about the size of traffic gaps rejected and accepted by pedestrians and the behaviour of riskier pedestrians (those adapting partial gap). The likelihood of pedestrians accepting gaps between vehicular traffic as a combination of different influencing independent variables such as traffic, environmental and personal factors was studied and modelled using logistic regression.

Formulation development and dissolution rate enhancement of efavirenz by solid dispersion systems.

The aim of this study was to enhance the dissolution rate of efavirenz using solid dispersion systems (binary and ternary). A comparison between solvent and fusion method was also investigated. Solid dispersions of efavirenz were prepared using polyethylene glycol 8000, polyvinylpyrrolidone K30 alone and combination of both. Tween 80 was incorporated to obtain a ternary solid dispersion system. Dissolution tests were conducted and evaluated on the basis of cumulative percentage drug release and dissolution efficiency. Physicochemical characterizations of the solid dispersions were carried out using differential scanning calorimetric, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. Dissolution was remarkably improved in both systems compared to pure efavirenz (P<0.05). An optimum ratio was identified at a drug:polymer of 1:10. Incorporation of Tween 80 to 1:10 formulations formed using solvent method showed further improvement in the dissolution rate. Physicochemical characterization results suggested that efavirenz existed in the amorphous form in all the solid dispersion systems providing evidence of improvement in dissolution. No statistically significant difference (P>0.05) in dissolution was observed between the two methods. Binary and ternary solid dispersion systems both have showed a significant improvement in the dissolution rate of efavirenz. Formulations with only polyvinylpyrrolidone K30 showed best dissolution profile and 1:10 was identified as an optimum drug-polymer weight ratio.

Young colorectal carcinoma patients do not have a poorer prognosis: a comparative review of 2,426 cases.

BACKGROUND: Colorectal cancer (CRC) in "young" patients under 50 years of age is uncommon. There have been conflicting reports regarding both the clinicopathological features of CRC in young patients and prognosis. The aim of this study was to review and compare the clinical characteristics, prognostic factors, and overall survival of patients in three different age groups (40 years and under, 41-50 years, over 50 years of age) and the prognosis of these patients. METHODS: A total of 2,426 consecutive patients who had undergone surgical resection for sporadic colorectal cancer at Singapore General Hospital in the period from 2000 to 2005 were retrieved from a prospectively collected computer database. There were 73 patients (3.0 %) in Group 1 (40 years old or less), 257 (10.6 %) in Group 2 (41-50 years old), and 2,096 (86.4 %) in Group 3 (>50 years old). Clinicopathological features were assessed using univariate analysis to evaluate significant differences, survival curves were constructed using the Kaplan-Meier method, and multivariate analysis was performed to evaluate the independent prognostic factors. RESULTS: Young CRC patients tend to present with a higher incidence of mucinous and signet ring cell tumors (Group 1-20.5 %, Group 2-8.2 %, Group 3-6.2 %, p < 0.001) and have more poorly differentiated tumors (Group 1-20.0 %, Group 2-9.7 %, Group 3-7.4 %, p = 0.014). Furthermore, young CRC patients tend to present with regional lymph node metastases (Group 1-65.7 %, Group 2-60.8 %, Group 3-51.0 %, p = 0.001) and distant metastases (Group 1-31.5 %, Group 2-24.1 %, Group 3-19.4 %, p = 0.006). Multivariate analysis reveals, however, that young age is not an independent prognostic factor for cancer-specific survival (CSS) (p = 0.392). Five-year CSS for Group 1 was 56.6 % (95 % confidence interval (CI) 44.8-68.4 %), Group 2 53.8 % (95 % CI 47.3-60.3 %), and Group 3 61.1 % (95 % CI 58.9-63.3 %). CONCLUSIONS: Although presenting with advanced tumors and with poorer prognostic factors such as presence of mucin and poor histological differentiation, young CRC patients do not have a worse prognosis.

Proteomic identification of proteins differentially expressed by nicotinamide in focal cerebral ischemic injury.

Nicotinamide exerts a potent neuroprotective effect against ischemia-induced brain injury. We identified proteins that were differentially expressed by nicotinamide treatment in ischemic brain injury. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats were treated with vehicle or nicotinamide (500 mg/kg) 2 h after the onset of MCAO. Brains were collected 24 h after MCAO and cerebral cortex regions were isolated. Protein spots with different intensities between vehicle- and nicotinamide-treated groups were detected using two-dimensional gel electrophoresis and identified by mass spectrometry. Among these proteins, γ-enolase, protein phosphatase 2A (PP2A) subunit B, and peroxiredoxin-2 (Prx-2) were significantly decreased in the vehicle-treated group compared to the nicotinamide-treated group. These identified proteins mediate cell differentiation and stabilization, and play a role as antioxidant enzymes. In contrast, 60 kDa heat shock protein (Hsp 60) was significantly increased in vehicle-treated animals, while nicotinamide prevented the injury-induced increase of this protein. These results suggest that nicotinamide mediates neuroprotective effects by up- and down-regulation of various specific proteins.

Vitamin C protects against ethanol and PTZ-induced apoptotic neurodegeneration in prenatal rat hippocampal neurons.

Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome, characterized by pre- and postnatal growth deficiencies, craniofacial anomalies, and evidence of CNS dysfunction. The objective of this study was to evaluate pentylenetetrazol (PTZ) and ethanol effects on Bax, Bcl-2 expression, which further induced activation of caspase-3, release of cytochrome-c from mitochondria, and to observe the protective effects of vitamin C (vit-C) against PTZ and ethanol-induced apoptotic neurodegeneration in primary-cultured neuronal cells at gestational day 17.5. Apoptotic neurodegeneration and neuroprotective effect of vit-C were measured by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay, Western blot analysis, which further conformed by the measurement of mitochondrial membrane potential using JC-1 detection kit and immunofluorescence analysis. The results showed that PTZ and ethanol produced extensive Bax-dependent caspase-9 and caspase-3 activation and caused neuronal apoptosis. Furthermore, the cotreatment of vit-C along with ethanol and PTZ showed significantly decreased expression of Bax, caspase-9, caspase-3, cytochrome-c, and significantly increased expression of antiapoptotic Bcl-2 protein when compared with control group. Our findings indicate that PTZ and ethanol activate an intrinsic apoptotic death program in neurons that is likely to contribute to the neuropathologic effects in fetal alcohol exposure, and vit-C can prevent some of the deleterious effects of PTZ and ethanol on the developing brain. The available experimental evidence and the safety of vit-C in pregnancy suggest the experimental use of ascorbic acid as a new and effective protective agent ethanol and PTZ-induced apoptotic neurodegeneration.

DNA methylation contributes to the tissue-specific expression of the rPL-Iv gene.

To understand the tissue-specific expression of the rat placental lactogen-I variant (rPL-Iv) gene, we investigated the methylation pattern of the 5'-flanking region of this gene in various rat tissues. We report that the 5'-flanking region of the rPL-Iv gene was hypomethylated in placenta that expressed the gene and hypermethylated in those tissues that did not express the gene. Moreover, the intron region of the rPL-Iv gene was hypomethylated in the placenta, but hypermethylated in the liver, kidney and pituitary. Although there are 5 CpG sites and the density of CpG dinucleotide is lower within 2 kb of the rPL-Iv 5'-flanking region, the methylated promoter reporter gene produced strong repression in the transcriptional activity of the gene. In addition, the 5'-flanking and intron regions of the rPL-Iv gene were hypomethylated on day 12 of gestation, and the methylation pattern in the placenta remained unchanged from mid-pregnancy until term. The entire genomic region of the rPL-Iv gene might be hypermethylated in tissues other than the placenta, within which its methylated status repress expression of the placenta-specific rPL-Iv gene. Interestingly, the methylation status of the intron region of the rPL-Iv in proliferating Rcho-1 cells was changed to the unmethylated status on day 8 and 12 of differentiation of Rcho-1 cells. These results demonstrate that demethylation in the rPL-Iv upstream region was induced at an early stage of placental development, and once the 5'-flanking region of the rPL-Iv had been demethylated, its status on the rPL-Iv genomic region was continued during pregnancy. Taken together, these results suggest that DNA methylation is responsible for the silencing of tissue-specific genes in non-expressing cells, while defined combinations of trophoblast factors dictate the expression of unmethylated rPL-Iv gene in placenta trophoblast cells.

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.