Phase I trials in patients with relapsed, advanced upper gastrointestinal carcinomas: experience in a specialist unit

Khan, Khurum; Ang, Joo Ern; Starling, Naureen; Sclafani, Francesco; Shah, Krunal; Judson, Ian; Molife, L. Rhoda; Banerji, Udai; Bono, Johann S. de; Cunningham, David; Kaye, Stan B.

doi:10.1007/s10120-013-0328-9

Cited by 7 publications

(8 citation statements)

References 23 publications

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“…The 75.7 % of patients with grade 3 or 4 adverse events is considerably higher than reported by previous analyses (19.7-39 %) [15,16]. A reasonable explanation is that the main NCI-CTEP-sponsored phase 1 trials for EGC were for combinations with biologic and cytotoxic agents.…”

Section: Discussioncontrasting

confidence: 45%

“…However, the impact of phase 1 treatment on safety and efficacy for patients with EGC has not yet been evaluated in a large population. Although the prognostic variables for OS have been analyzed [15], the usefulness of the RMH prognostic score for EGC patients has not yet been evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…There have been few analyses of clinical benefits and prognoses for EGC patients who were registered in phase 1 trials [15,16]. Those analyses assessed the toxicities, treatment-related trial discontinuations, and efficacies.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials

et al. 2016

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Background In phase 1 trials, an important entry criterion is life expectancy predicted to be more than 90 days, which is generally difficult to predict. The Royal Marsden Hospital (RMH) prognostic score that is determined by lactate dehydrogenase level, albumin level, and number of metastatic sites of disease was developed to help project patient outcomes. There have been no systematic analyses to evaluate the utility of the RMH prognostic score for esophagogastric cancer patients. Methods All nonpediatric phase 1 oncology trials sponsored by the National Cancer Institute Cancer Therapy Evaluation Program that began between 2001 and 2013 were considered in this review.Results Of 4722 patients with solid tumors, 115 patients were eligible for our analysis; 54 (47 %) with cancer of the esophagus, 14 (12 %) with cancer of the esopagogastric junction, and 47 (41 %) with stomach cancer. Eighty-six patients (75 %) had a good RMH prognostic score (0 or 1) and 29 patients (25 %) had a poor RMH prognostic score (2 or 3). Disease control rates were significantly different between patients with good and poor RMH prognostic scores (49 % vs 17 %; two-sided Fisher's exact test P = 0.004). The median treatment duration and overall survival for good and poor RMH prognostic score patients were significantly different (median treatment duration 2.1 months vs 1.2 months respectively, P = 0.016; median overall survival 10.9 months vs 2.1 months respectively, P \ 0.001). In the multivariate analysis, age (60 years or older), Eastern Cooperative Oncology Group performance status (2 or greater), and the RMH prognostic score (2 or 3) were significant predictors of poor survival. Conclusions The RMH prognostic score is a strong tool to predict the prognosis of esophagogastric cancer patients who might participate in a phase 1 trial.

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Section: Discussioncontrasting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

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Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials

et al. 2016

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“…Phase I clinical trials are traditionally considered as a means of establishing the maximum tolerated dose of anticancer therapies. However, with the advent of molecularly targeted therapeutics and mapping out of the underlying biology of different cancers and antitumor agents, they may now represent bona fide trial options that may be of benefit, subgroups of patients who have failed all standard available anticancer therapies irrespective of their age ( Khan et al , 2014 ). The lack of representation of older patients with advanced cancers in clinical trials is widely reported ( Hutchins et al , 1999 ; Talarico et al , 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Phase I trial outcomes in older patients with advanced solid tumours

Khan¹,

Yap²,

Molife³

et al. 2016

Br J Cancer

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Background:This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients.Methods:Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity and clinical outcome data were compared between patients aged below and above 65 years of age.Results:One thousand and four patients were treated in 30 Phase I trials, with 315 (31%) patients aged 65 years and older. Grade 3–5 toxicities (22.8% vs 24.8% (P=0.52)), trial discontinuation (6% vs 4% P=0.33), and dose interruptions (8.0% vs 8.0% (P=0.96)) were observed at similar rates in patients below and above 65 years of age, respectively. The overall response rate 5.2% vs 4.1%, progression-free survival (PFS) 1.9 vs 3.5 months and clinical benefit rate (CBR) at 6 months 15.2% vs 14.3% were comparable in both groups. To avoid bias due to the potential therapeutic benefit of abiraterone, comparisons were repeated excluding prostate cancer patients with similar results (ORR 4.6% vs 4%, PFS 1.8 vs 3.0 months, CBR at 6 months 13.5% vs 9.5%). Multivariate analysis indicated that the previously identified RMH score (including albumin and lactate dehydrogenase levels) was an accurate predictor of outcome.Conclusions:Phase I clinical trials should be considered in patients with advanced cancers regardless of age, as older patients who enter these have similar safety and efficacy outcomes as their younger counterparts. The RMH prognostic score can assist in the selection of suitable older patients.

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“…Our series was in agreement with these established findings; additionally we found that low albumin and abnormal platelet count were prognostic of worse outcome for both PFS and OS. Abnormal platelet count has been considered as an important prognostic factor in CRC based on the data from UK COIN study [ 30 ], whilst we have previously reported an association of abnormal albumin with poor outcomes in upper GI cancers [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors and treatment outcomes in patients with Small Bowel Adenocarcinoma (SBA): The Royal Marsden Hospital (RMH) experience

et al. 2015

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BackgroundSBA is a rare tumour which carries a poor prognosis. Very few data on prognostic factors and treatment outcomes are available. We conducted a retrospective analysis of patients treated for SBA at our institution.MethodsClinico-pathological characteristics, treatments and outcomes of all the SBA patients treated consecutively from 1996 to 2011 were retrospectively collected. The prognostic value of baseline factors was assessed using the Cox regression model. The Kaplan-Meier method was used to estimate the survival outcomes.ResultsEighty-four patients with SBA were treated during the study period. Of these, 48 presented with early stage SBA, while 36 had unresectable disease. All early stage SBA patients (58.3% males; median age, 59 years) underwent resection (R0 in 44/48) and 27 (56%) received adjuvant chemotherapy. Median relapse-free survival and overall survival (OS) were 31.1 months (95% CI: 8.0-54.3) and 42.9 (95% CI: 0–94.9), respectively. In univariate analyses, poor histological differentiation (p = 0.025) and lymphovascular invasion (p = 0.003) were prognostic for OS. In the group of patients with relapsed, unresectable or metastatic disease (n = 59), systemic chemotherapy was administered in 46 cases (78%). The response rate to first line chemotherapy was 50%. Median progression-free survival and OS were 8.8 (95% CI: 5.5-12.3) and 12.8 months (95% CI: 8.4-17.2), respectively. In univariate analyses, low albumin (p = 0.041) and high platelet count (p = 0.007) were prognostic for OS.ConclusionProspective clinical trials are needed to inform the management of SBA patients. Prognostic factors evaluated in our series may be useful for patient stratification and treatment selection in future studies.

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Phase I trials in patients with relapsed, advanced upper gastrointestinal carcinomas: experience in a specialist unit

Cited by 7 publications

References 23 publications

Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials

Analysis of esophagogastric cancer patients enrolled in the National Cancer Institute Cancer Therapy Evaluation Program sponsored phase 1 trials

Phase I trial outcomes in older patients with advanced solid tumours

Prognostic factors and treatment outcomes in patients with Small Bowel Adenocarcinoma (SBA): The Royal Marsden Hospital (RMH) experience

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