Showing papers by "Thomas Powles published in 2012"
TL;DR: Cisplatin-based neoadjuvant combination chemotherapy is an established standard, improving overall survival in MIBC and pathologic complete response appears to be an intermediate surrogate for survival, but this finding requires further validation.
220 citations
TL;DR: The data suggest that the effects of sunitinib on tumour progression are dose-dependent and tumour model-dependent, and have relevance for understanding how anti-angiogenic agents may influence disease progression when used in the adjuvant or metastatic setting in cancer patients.
Abstract: Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metastases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastases in Balb/c mice, to re-address the effects of sunitinib on the progression of metastatic disease in mice. We show that treatment of mice with sunitinib prior to intravenous injection of tumour cells can promote the seeding and growth of 4T1 lung metastases, but not RENCA lung metastases, showing that this effect is cell line dependent. However, increased metastasis occurred only upon administration of a very high sunitinib dose, but not when lower, clinically relevant doses were used. Mechanistically, high dose sunitinib led to a pericyte depletion effect in the lung vasculature that correlated with increased seeding of metastasis. By administering sunitinib to mice after intravenous injection of tumour cells, we demonstrate that while sunitinib does not inhibit the growth of 4T1 lung tumour nodules, it does block the growth of RENCA lung tumour nodules. This contrasting response was correlated with increased myeloid cell recruitment and persistent vascularisation in 4T1 tumours, whereas RENCA tumours recruited less myeloid cells and were more profoundly devascularised upon sunitinib treatment. Finally, we show that progression of 4T1 tumours in sunitinib treated mice results in increased hypoxia and increased glucose metabolism in these tumours and that this is associated with a poor outcome. Taken together, these data suggest that the effects of sunitinib on tumour progression are dose-dependent and tumour model-dependent. These findings have relevance for understanding how anti-angiogenic agents may influence disease progression when used in the adjuvant or metastatic setting in cancer patients.
62 citations
TL;DR: A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway.
Abstract: BACKGROUND:
Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway.
METHODS:
Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy.
RESULTS:
All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively.
CONCLUSIONS:
AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials.
44 citations
TL;DR: Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option for mRCC and PFS and tolerability were similar for first-line EVE +-BEV and IFN + BEV.
31 citations
TL;DR: Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit, but the optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed.
Abstract: With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib–sunitinib vs. sunitinib–sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib–everolimus vs. everolimus–sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.
28 citations
TL;DR: The evidence for targeted treatment in both the neoadjuvant and adjuvant setting, and its use with cytoreductive nephrectomy, is summarized.
Abstract: Locally advanced renal cell cancers have a significant recurrence rate following radical nephrectomy. Traditional cytotoxic chemotherapy and immunotherapy have failed to demonstrate a benefit in the adjuvant setting. Recent advances in the treatment of metastatic renal cell carcinoma using agents that target VEGF and the mTOR pathways have radically changed the way metastatic renal cell carcinoma is treated. These drugs may be able to reduce the rate of recurrence in high-risk disease, and are now being assessed in the neoadjuvant and adjuvant settings. This review summarizes the evidence for targeted treatment in both the neoadjuvant and adjuvant setting, and its use with cytoreductive nephrectomy.
18 citations
TL;DR: Sunitinib and pazopanib are widely used as first-line therapy in metastatic renal cancer (mRCC) and the efficacy of these agents appears similar but they may have distinct toxicity profiles.
16 citations
TL;DR: Current arguments for Cytoreductive nephrectomy and how to best select patients for surgery are summarized, suggesting that some patients may benefit substantially from CN in the era of targeted therapy.
Abstract: Renal cell carcinoma presents with metastatic disease in approximately 30% of patients at the time of diagnosis. Cytoreductive nephrectomy (CN) of the primary tumor in the face of metastatic disease is part of a multimodality approach including systemic therapy that is based on evidence from randomized trials in the cytokine era. Data from the pretargeted therapy era showed that CN had a clear role in metastatic renal cell carcinoma, increasing life expectancy by approximately 6 months. The substantial improvement in outcomes reported for targeted therapy has challenged the previous role of CN. However, despite the absence of data from Phase III trials, available evidence suggests that some patients may benefit substantially from CN in the era of targeted therapy. This review summarizes current arguments for CN and how to best select patients for surgery. Ongoing trials are key in generating evidence towards a personalized approach to debulking nephrectomy.
14 citations
TL;DR: CRN after treatment with sunitinib is safe and feasible in the hands of surgeons, although the surgery is more time-consuming and technically demanding.
Abstract: Objective: To describe for surgeons contemplating performing cytoreductive nephrectomy (CRN) on patients after neoadjuvant sunitinib compared to a benchmark of op
12 citations
TL;DR: Treatment guidelines and trials evaluating targeted agents for mRCC are reviewed to assess the evidence regarding commencing and discontinuing therapy for m RCC.
10 citations
TL;DR: Autologous transplantation following high-dose alkylating agent chemotherapy induces responses but proved toxic, although dose escalation proved possible and the possibility of using CTCs to identify responders at two weeks may be used to justify such an intensive approach.
Abstract: Purpose: Nontaxane-based chemotherapeutic options in castrate-resistant prostate cancer (CRPC) are limited despite the long natural history of the disease. We carried out a phase 1 dose-escalation study of the alkylating agent melphalan with autologous stem cell transplantation, comparing rapid changes in circulating tumor cells (CTC) and prostate-specific antigen (PSA) as a measure of response. Experimental Design: Cohorts of individuals with advanced CRPC received high-dose intravenous melphalan, and autologous blood was returned to patients during treatment. The efficacy endpoints were the PSA reduction rate, CTC response, survival parameters, toxicity and whether reinduction of endocrine sensitivity occurred. Results: Twenty-four patients were recruited. Dose escalation was feasible with the highest dose cohort being reached. Of 23 individuals evaluable for response, 16 had a PSA response of more than 30%; of 11 patients with soft tissue disease, 4 achieved a partial response and 7 had stable disease. Patients with CTC counts that decreased to less than 5 within 2 weeks from the start of therapy had a longer overall survival (30.6 months vs. 15.3 months, P = 0.03) Treatment was associated with myelosuppression and frequent hospitalizations. In 20 patients after the study, hormone therapy was reintroduced when PSA increased again; response rates were high. Conclusions: Autologous transplantation following high-dose alkylating agent chemotherapy induces responses but proved toxic, although dose escalation proved possible. The possibility of using CTCs to identify responders at two weeks may be used to justify such an intensive approach. Many individuals went on to further respond to both docetaxel and hormonal therapy. Clin Cancer Res; 18(8); 2352–9. ©2012 AACR .
TL;DR: This efficacy and toxicity profile appeared to result in a benefit for axitinib compared with sorafenib in composite quality of life scores, and axitinib is clearly an active and tolerable agent.
TL;DR: Protein expression in ccRCC is heterogenous and key proteins showed significantly increased variance of expression with sunitinib therapy, despite heterogeneity, significant changes in protein expression can be identified with sun itinib treatment and have been correlated with outcome.
Abstract: 388 Background: To investigate acquired resistance of clear cell renal cell cancer (ccRCC) patients to sunitinib and develop personalised treatment strategies, sequential tissue after a specific period of targeted therapy is required. This approach has proven successful with targeted therapy in chronic myeloid leukaemia; however, we are concerned that extensive tumour heterogeneity occurs in ccRCC. In this study we evaluated heterogeneity and differential protein expression in sunitinib treated and untreated ccRCC samples using high-throughput proteomics. Methods: Fresh frozen tissue was obtained from 27 sunitinib naive ccRCC specimens and 27 nephrectomy samples from patients treated with neoadjuvant sunitinib (18 weeks) as part of the SuMR trial. From each tumour frozen sections were performed and up to 5 protein lysates obtained from each morphologically differing region of each tumour as well as matched normal kidney. Reverse phase protein arrays (RPPA) were performed to assess the levels of multiple p...
TL;DR: A prospective global randomised trial comparing conventional dose therapy and triple high dose therapy (paclitaxel and ifosamide followed by high dose carboplatin and etoposide [TI CE]) is planned for 2012 and it is hoped it will finally address this area major of uncertainty in GCTs.
Abstract: Patients with relapsed germ cell tumors (GCT) are potentially curable despite the failure of initial cisplatin based therapy. The recent identification of robust prognostic markers has helped clarify this area of uncertainly [17••]. However, unlike the initial treatment of metastatic disease where cisplatin based combination therapy is standard of care, there is no consensus on treatment in the relapsed setting [28]. Instead there is a genuine equipoise between high dose therapy (HDCT) and conventional dose therapy (CDCT) in this relapsed setting [17••]. The randomised data fails to support the use of HDCT although retrospective analysis consistently shows it may be superior, especially if tandem or triple high dose therapy is used [26]. This has resulted in different approaches worldwide with some stating HDCT should not be used outside of a trial and others suggesting it is standard of care [5, 29]. Re-challenging relapsed patients with conventional dose cisplatin based therapy would seem to be counterintuitive, but the addition of drugs such as ifosamide and paclitaxel results in genuine activated in selected patients with relapsed disease [8]. This appears particularly relevant as HDCT is associated with significant morbidity and mortality, which was highlighted in a randomised trial [16, 26]. However large single institution data suggests this treatment related toxicity may not be such as concern and treatment related mortality can be as low as only 3 % in selected centres [5]. Overall there is a need to answer this question of CDCT v.s. HSCT definitively. For this reason a prospective global randomised trial (TIGER trial) comparing conventional dose therapy (paclitaxel, ifosamide and cisplatin [TIP]) and triple high dose therapy (paclitaxel and ifosamide followed by high dose carboplatin and etoposide [TI CE]) is planned for 2012 (TIGER trial). Due to the rarity of this disease and complexities associated with a global trial, this study faces many challenges. Nevertheless it is hoped that it will finally address this area major of uncertainty in GCTs.
TL;DR: Liver toxicity in patients treated with pazopanib occurs in 1/3 of patients, usually in the first 12 weeks of therapy, and management is facilitated by blood monitoring, temporary cessation of therapy and dose reductions.
TL;DR: Bone metastasis in GCT is rare, and is believed to confer poor prognosis, and this series of patient outcomes following standard first-line platinum based chemotherapy is small but appears to support this conclusion.
Abstract: 343 Background: Metastasis of testicular germ cell tumour (GCT) to bone is a rare event and there is little evidence on optimal curative management. Methods: A retrospective review of case records of germ cell tumour patients within the Anglian Germ Cell Cancer Group between 10/01/2005 and 14/03/2011 was conducted. Results: 2,550 cases of testicular germ cell tumour were reviewed and 19 patients with bone metastases were identified, median age 38yrs. Average duration of follow-up was 21.7 months. Most were NSGCT (11/19), or seminoma (3/19). Five patients were treated on the basis of markers alone. Bone metastases present at diagnosis 12/19, and diagnosed at relapse/progression in 6/19 cases. Bony metastases were most commonly found in the vertebrae (15/19), pelvis (5/19) and ribs (3/19). In 10 cases a single bone metastasis was found, in 9 cases multiple areas of bone metastasis occurred. The imaging modality diagnostic of bone metastases was most frequently CT scan (11/19), FDG-PET (4/19) or MRI (3/19). ...
TL;DR: The findings from AXIS, RECORD-1, and the International mRCC Database Consortium do not support the hypothesis that switching mode of action from VEGF inhibition to mTOR is the logical first step in the face of V EGF resistance, and suggest that pre-treatment with effective VEGf-TKI therapy, such as sunitinib, has a detrimental effect on subsequent outcome with both VEGFs-tKI therapy and mTOR inhibition.
Abstract: Metastatic renal cell carcinoma (mRCC) is a fast-moving therapeutic field with multiple targeted agents approved and many more in development. In our expert agreement article [1], we evaluated available data together with our clinical experience to consider how we might optimize using targeted therapies in sequence, emphasizing the need continually to address the question, ‘‘what comes next?’’ Crucially, new phase III data presented at the American Society of Clinical Oncology (ASCO) 2011 annual meeting provide level 1 evidence that patients can receive continued clinical benefit when VEGF-targeted tyrosine kinase inhibitors (TKIs) are used sequentially [2, 3]. The randomized, open-label, phase III AXIS study compared second-line axitinib 5 mg bid (titrated to 7, then 10 mg bid, if tolerated) with sorafenib 400 mg bid in 723 patients with mRCC, more than half of whom had previously received the TKI sunitinib (n = 389) [2]. The study met the primary endpoint of superiority for axitinib, with median PFS 6.7 months, compared with 4.7 months for sorafenib (P \ 0.0001). Median PFS was lower in post-sunitinib than in the total patient population for both axitinib (4.8 months) and sorafenib (3.4 months; P \ 0.05 versus axitinib). Notably, and as discussed in our expert agreement article, this phenomenon was also seen in the phase III RECORD-1 study of everolimus in patients previously treated with sorafenib and/or sunitinib—prior sunitinib was prognostic of lower PFS and overall survival in a multivariate analysis [1]. The AXIS and RECORD-1 data, therefore, suggest that pre-treatment with effective VEGF-TKI therapy, such as sunitinib, has a detrimental effect on subsequent outcome with both VEGF-TKI therapy and mTOR inhibition. Therefore, cross-resistance between these two classes may be apparent. A further noteworthy publication at ASCO 2011, from Dr. Mhd Al-Marrawi on behalf of the International mRCC Database Consortium, showed that response to initial TKI therapy did not predict response to further TKI therapy [4]. This study did not report whether the sequence of TKIs received was important, but this question could be addressed in part by performing a similar analysis using the AXIS data—i.e., were ORR/stable disease/PFS with axitinib or sorafenib related to ORR/stable disease/PFS with sunitinib and were there differences between axitinib and sorafenib in this regard? Overall, the findings from AXIS, RECORD-1, and the International mRCC Database Consortium do not support the hypothesis that switching mode of action from VEGF inhibition to mTOR is the logical first step in the face of VEGF resistance. Re-challenging with VEGF-TKI therapy appears to be more attractive as the first treatment manipulation at present. Switching to mTOR as 3rd line or later, which is supported by randomized phase III data, gives us multiple lines of therapy with proven efficacy. On a further note, though it may be tempting to compare the efficacy data from AXIS with those for RECORD-1, there are a number of key differences between the studies, including patient population and study design, and so such comparisons are fundamentally flawed. Patient-reported outcomes from AXIS were also presented at ASCO [3]. Dr. David Cella showed that C. Porta (&) I.R.C.C.S. San Matteo University Hospital Foundation, Pavia, Italy e-mail: c.porta@smatteo.pv.it
TL;DR: The prognosis of patients with stage I non-seminomatous germ cell tumors is in general very good, however, a large number of patients relapse with metastatic disease after orchidectomy, so adjuvant treatment, in the form of either chemotherapy or retroperitoneal dissection is recommended.
Abstract: The prognosis of patients with stage I non-seminomatous germ cell tumors is in general very good. However, a large number of patients relapse with metastatic disease after orchidectomy Therefore, adjuvant treatment, in the form of either chemotherapy or retroperitoneal dissection is recommended, although active surveillance has been found to be as good a way of treating these patients with overall excellent results.
TL;DR: There are multiple treatment options for patients in the first and second line setting due to difficulty distinguishing between targeted therapies due to lack of head to head studies.
Abstract: Currently 7 targeted therapies have been approved for the treatment of advanced RCC: sorafenib, sunitinib, temsirolimus, axitinib, bevacizumab in combination with interferon-α, everolimus and pazopanib (1). There is difficulty distinguishing between them due to lack of head to head studies. Therefore there are multiple treatment options for patients in the first and second line setting.
TL;DR: There is concern that interruption of tyrosine kinase inhibitors (TKI) triggers disease progression (PD) and metastasis and this is based on preclinical models and observation of rapi...
Abstract: 4611 Background: There is concern that interruption of tyrosine kinase inhibitors (TKI) triggers disease progression (PD) and metastasis. This is based on preclinical models and observation of rapi...
TL;DR: There is no consensus among UK clinicians regarding optimum post-operatively treatment of muscle invasive utTCC, and the POUT trial offers the opportunity to standardise post-operative management of utT CC internationally and is supported by urologists, oncologists and consumer representatives from the target patient population.
TL;DR: TKIs targeting HER1-4 receptors had a clear effect on the viability of bladder cancer cells, and dual (Lapatinib) and pan (Canertinib) -HER inhibitors were more potent than the single HER inhibitors Gefitinib and CP-724714.
Abstract: Introduction: The survival of patients with invasive bladder cancer is short, suggesting an urgent need for new treatments. Given that HER family receptor tyrosine kinases (TK) are associated with tumor stage/grade and outcome in this malignancy (Chow et al, Clin Cancer Res, 2001), approaches using small molecule inhibitors of HER receptors may be of value. In the present study we have investigated the potential utility and mechanism of action of Gefitinib (HER1 inhibitor), CP-724714(HER2 inhibitor), Lapatinib(dual HER1/2 inhibitor) and Canertinib (pan-HER inhibitor) in a panel of human bladder cancer cell lines. Methods: Four bladder cancer cell lines were used (T24, J82, H1376, 647V). HER 1-4 receptor protein and transcript were determined by Western blot and RT-PCR respectively. An ATP assay was used to determine the cytotoxic effect of HER targeted TKIs, with effects on cell cycle distribution and apoptosis determined by flow cytometric methods. A cell line with high receptor expression was selected for RNAi-silencing experiments targeting HER2 using lentivectors to determine the effects of specific HER2 silencing compared to the effects of HER2 inhibition. The differential effects of HER2 inhibition or silencing on downstream signalling was studied using western blot analysis and LC-MS/MS based methods for Akt activity and phosphoprotein profiling. Results: The expression levels of HER1-4 members varied between the cell lines. Sensitivity to TKIs also varied and was not correlated with HER1-4 expression. However, the dual (Lapatinib) and pan (Canertinib) -HER inhibitors were more potent (up to 30-fold) than the single HER inhibitors Gefitinib and CP-724714. Cell cycle analysis typically showed an increase in the G2/M population with all treatments, with a clear increase in apoptotic cells (up to 70%) observed only with Lapatinib. RNAi mediated HER2-knockdown in T24 cells was confirmed by western blotting and RT-PCR. With the exception of Gefitinib, sensitivity to TKIs was not altered by HER2 knockdown, with EC50 values for the HER2 TKI CP-724714 in parental and HER2-knockdown cells of 36.4 ± 14.5 vs 31.5 ± 10.3 µM respectively. Both HER2 RNA-silencing and inhibition by TKIs resulted in decreased downstream signalling (40% and 70% respectively), based on PI3K activity and phosphorylation of AKT. Phosphoproteomic analysis of TKI inhibited or HER2-knockdown cells showed common phosphoproteins (AHNAK, ASF-1) that were altered with all treatments, and others that were specific for HER2 silencing, HER2 TKI or HER2 mAb (Trastuzumab) exposure. Similar studies are now being performed in a second cell line. Conclusions: TKIs targeting HER1-4 receptors had a clear effect on the viability of bladder cancer cells. Both HER2-RNA silencing and TKIs resulted in decreased PI3K pathway activity. Phosphoproteins altered by these treatments highlight specific kinases that might represent potential therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1792. doi:1538-7445.AM2012-1792
01 Jan 2012
TL;DR: The data suggest that the effects of sunitinib on tumour progression are dose- dependent and tumour model-dependent, and have relevance for understanding how anti-angiogenic agents may influence disease progression when used in the adjuvant or metastatic setting in cancer patients.
Abstract: Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metas- tases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastases in Balb/c mice, to re-address the effects of sunitinib on the pro- gression of metastatic disease in mice. We show that treatment of mice with sunitinib prior to intravenous injection of tumour cells can promote the seeding and growth of 4T1 lung metastases, but not RENCA lung metastases, showing that this effect is cell line dependent. However, increased metastasis occurred only upon administration of a very high sunitinib dose, but not when lower, clinically relevant doses were used. Mechanistically, high dose sunitinib led to a pericyte depletion effect in the lung vasculature that correlated with increased seeding of metastasis. By administering sunitinib to mice after intra- venous injection of tumour cells, we demonstrate that while sunitinib does not inhibit the growth of 4T1 lung tumour nodules, it does block the growth of RENCA lung tumour nodules. This contrasting response was correlated with increased myeloid cell recruitment and persistent vascu- larisation in 4T1 tumours, whereas RENCA tumours recruited less myeloid cells and were more profoundly devascularised upon sunitinib treatment. Finally, we show that progression of 4T1 tumours in sunitinib treated mice results in increased hypoxia and increased glucose metab- olism in these tumours and that this is associated with a poor outcome. Taken together, these data suggest that the effects of sunitinib on tumour progression are dose- dependent and tumour model-dependent. These findings have relevance for understanding how anti-angiogenic agents may influence disease progression when used in the adjuvant or metastatic setting in cancer patients.
01 Jan 2012
01 Jan 2012
TL;DR: Harshman et al. as discussed by the authors suggested that PFS might not be a useful marker in prediction of outcome, questioning present trial design and suggesting that the addition of newer agents to the range of drugs available for treatment on the basis of PFS advantage might only confuse the situation further.
Abstract: 860 wwwthelancetcom/oncology Vol 13 September 2012 seem out of reach Randomised data suggests PFS might not be a useful marker in prediction of outcome, questioning present trial design The addition of newer agents to the range of drugs available for treatment on the basis of PFS advantage might only confuse the situation further A wiser approach might be to find better ways of using what is already available to us, with novel trial design and analysis Harshman and colleagues’ data is a practical step in this direction