tbuckley/cabot-search huggingface dataset:
Capecitabine and oxaliplatin: A phase II study with a new schedule of administration in elderly patients with advanced colorectal cancer
Authors: A. Comandone, P. Pochettino, P. Bergnolo, A. Boglione, O. Dal Canton, S. Chiado Cutin, F. Garetto, M. Biscardi, C. Oliva
Journal: Journal of Clinical Oncology (2005)

3681 Background: Oral Capecitabine (CAP) is a highly effective chemotherapy agent for treatment of advanced colorectal cancer (ACRC), demonstrating superior antitumour activity and an improved safety profile versus 5-FU/LV. CAP moreover enables chronic dosing that mimics continuous infusion 5-FU and generates 5-FU preferentially in tumor via increased expression of thymidine phosphorylase. Oxaliplatin (OHP) is a third generation platinum compound with activity against colorectal cancer. Since adding OHP to infused 5-FU/LV improves efficacy, and substituting CAP for 5-FU/LV in combination with OHP should give effective, safe and convenient treatment. On the basis of the results of XELOX trial (Van Cutsem, 2003) we tested a regimen with CAP continuously (Cunningham, 2003) in elderly patients. Methods: On January 2003 we started a mono-institutional study with the following schedule: OHP 50 mg/sqm on days 1, 8, 15, 22 every 35 and CAP 1000 mg/sqm/day continuosly. End points of the study were feasibility, response rate and toxicity. Main elegibility criteria: ACRC untreated or pretreated; age ≥ 65 years, PS ECOG 0–2; an adequate hematologic, hepatic and renal function. 27 pts (17 M, 10 F) entered the study. Median age was 71 (65–79), median PS ECOG was 1. The primary tumour was colon cancer in 23 pts and rectal cancer in 4 pts. The sites of relapse were (one or more) 21 hepatic, 4 lung, 4 peritoneum, 2 abdominal nodes. 8 patients were pretreated with a first line chemotherapy and 4 received a previous radioterapy. Results: All patients were evaluable for toxicity and 26 for response. Following the RECIST criteria we observed: 5 PR (19,2%), 9 SD (34,6%), 12 PD (46,2%); 3 pts underwent surgical resection of their relapsing disease (hepatic) and conducted to a CR; median TTP was 6.1 monhts and OS was 14.2 months. Toxicity was very low: GI/II peripheral neuropathy in 11 pts (40%), G I/II nausea-vomiting in 5 pts (18%), G I/II neutropenia in 7 pts (26%), GI/II asthenia 10 pts (35%). In one case the treatment was interrupted for toxicity (neuropathy G III after 1 course). Conclusion: This regimen is feasible, active and very safe in elderly patients with ACRC; no life threatening toxicities were registered. No significant financial relationships to disclose.
Application of active surveillance threshold to series of samples submitted for commercial testing.
Authors: Peter T. Scardino, Jack M. Cuzick, Steve Stone, Brent Evans, Matthew R Jorgensen, James Andrew Eastham, Thomas E. Keane, John W. Davis, Daniel W. Lin, Judd W. Moul, Michael K. Brawer, E. David Crawford
Journal: Journal of Clinical Oncology (2016)

84 Background: Active surveillance (AS) is an increasingly popular treatment modality for men with localized prostate cancer. Recently, we developed a method to select men for AS based on a score that combines cell cycle progression (CCP) with CAPRA (combined clinical CCP risk (CCR) score). Here, we apply our validated AS threshold to a series of samples submitted for commercial testing. Methods: Formalin-fixed prostate biopsy samples from 7,881 patients were submitted by their physicians to Myriad Genetic Laboratories for CCP analysis. Patient clinicopathological data was obtained from the test request form. The CCP score was calculated based on RNA expression of 31 CCP genes normalized to 15 housekeeping genes, and combined with CAPRA to generate the CCR score. The clinicopathological data of patients with a CCR score meeting the AS threshold were analyzed focusing on their PSA, % positive cores, Gleason, stage, AUA risk classification, and CAPRA score. Results: Of the 7,881 patients included in the analysis, 4,758 (60.4%) qualified for AS based on their CCR score. A substantial number of these patients, 2,213 (46.5%), would not have qualified for AS based on their clinical characteristics alone according to the following criteria: Gleason ≤ 3+4, PSA &lt; 10, clinical stage ≤ T2a, and &lt; 25% positive cores. A summary of the patients’ clinicopathological characteristics is shown below. Conclusions: This analysis showed that 60.4% of commercially tested patients qualified for AS, nearly half of which would not have qualified for AS based on their clinicopathological characteristics. For patients considering deferred treatment, the CCR score provides significant prognostic information at disease diagnosis. [Table: see text]
Surrogate markers of activity of AG-013736, a multi-target tyrosine kinase receptor inhibitor, in metastatic renal cell cancer (RCC)
Authors: O. Rixe, J.-B. Meric, J. Bloch, A. Gentile, R. Mouawad, V. Adam, D. Buthiau, D. Khayat
Journal: Journal of Clinical Oncology (2005)

3003 Background: Significant activity of AG-013736, an oral small molecule with potent inhibitory effects against the VEGF receptors 1 (VEGFR-1) and 2 (VEGFR-2) and PDGF receptor, is reported in a phase 2 study in metastatic RCC (Rini D. et al, ASCO 2005). Over the 52 enrolled patients (pts), best response assessed by RECIST criteria is 40% (21 partial responses. However, the frequency of stable disease and clinical improvement lead to define new parameters of therapeutic evaluation. The question was addressed in 13 patients treated in Salpêtrière Hospital, included in this phase 2 study. Ancillary studies were conducted to monitor (i) vascular tumour flow using qualitative and quantitative CT perfusion for visceral and non-visceral metastases (ii) biological effect of the anti-angiogenic therapy including soluble proteins involved in the angiogenic pathway. Methods: To calculate various tumours perfusion parameters, regional blood flow and volume, mean transit time, hepatic arterial fraction were determined with General Electric’s CT Perfusion Program. Serum were collected pre- and 1, 2, 4, 6-months post AG-013736 treatment initiation and analysed by ELISA tests for VEGFs, VEGFR-1, VEGFR-2. Results: Decreased tumour perfusion (TP) was observed in patients responding to therapy, including liver metastases. Furthermore, in 4 out of 6 patients with stable or progressive disease by RECIST, decreased TP was strongly correlated with clinical improvement. No relation was observed in this cohort between responders (RECIST criteria, n=7 pts), non-responders (n=6) and biological parameters (VEGFs, VEGFR-1, VEGFR-2). Conclusion: Conventional RECIST criteria were designed as a tool for evaluating cytoxic agents. New tools, such as the quantification of tumor blood flow, may yield additional information in the evaluation of anti-angiogenic therapy for solid tumours. Although this observation is based on the data from a small number of patients, this preliminary finding leads us to believe that TP is a useful parameter in evaluating disease status. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer
Sequential chemotherapy with gemcitabine plus carboplatin followed by additional docetaxel for older patients with advanced bladder cancer.
Authors: Takahiro Yoneyama, Naoki Sugiyama, Yuuichirou Suzuki, Akiko Okamoto, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2013)

266 Background: We retrospectively evaluated the feasibility and effectiveness of a sequential chemotherapy wihtout cisplatin for the patients 70 years or older with advanced bladder cancer. Methods: Fourty-seven patients with advanced bladder cancer (33 men and 14 women) with the age of 70 years or older were enrolled. They were treated at our clinic between August 2004 and December 2010. Their average age was 80.0 years old (70–86), average Ccr was 37.0 ml/min (14.5–113.0), and an average follow-up period was 17.4 months (10–55). There were 15 recurrent cases after radical surgery and 32 inoperable cases (T4b or metastatic). As for prior chemotherapy, 6 underwent MVAC therapy. The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. If this regimen was effective, another 2 courses of GCarbo was performed. Treatment efficacy was checked every 2 course according to the RECIST version 1.1. Results: Of the 47 subjects who had undergone the GCarbo therapy, the response rate was 38.3% (CR+PR) with 5 and 12 subjects exhibiting a complete response (CR) and a partial response (PR), respectively; the average response duration was 15.7 months (2–42). Of the subjects with MVAC resistance, 1 exhibited a CR and 3 showed a PR. The response rates of 9 instances of GCarboD was 11.1%; the overall median survival was 15.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 30 of those who had undergone the GCarbo therapy (63.8%). Conclusions: Although the present study is small and preliminary, the present sequential chemotherapy is safe and active for advanced bladder cancer of the patients seventy years or older. GCarbo regimen achieved acceptable response rate (38.3%) in advanced bladder cancer including M-VAC-resistant case. The median overall survival of 15 months is acceptable when average age of 80 year for the subjects is took into consideration. However, GCarboD had limited effectiveness for non-responder of GCarbo.
Does abiraterone withdrawal syndrome (AWS) exist also in metastatic castration-resistant prostate cancer (mCRPC) first-line setting?
Authors: Francesca Maines, Orazio Caffo, Chiara Trentin, Antonello Veccia, Enzo Galligioni
Journal: Journal of Clinical Oncology (2016)

344 Background: AWS is a recently phenomenon observed in mCRPC patients (pts) characterized by a PSA reduction with or without objective response after abiraterone acetate (AA) discontinuation. This syndrome has clinical features similar to antiandrogen withdrawal syndrome and was described in pts who treated with AA in the post-docetaxel setting. At the best of our knowledge, to date AWS was never described in chemo-naïve mCRPC pts. Methods: We retrospectively reviewed clinical records of mCRPC pts treated with first-line AA at our Institution. All pts were treated with AA 1,000 mg + prednisone (PDN) 10 mg po daily; the treatment was continued until progression disease (PD) which required an imaging confirmation too. After PD, we also discontinued the PDN administration. For each pt we recorded pre and post-AA clinical history, treatment details and outcomes. AWS was defined by PSA reduction ≥ 25% compared to the AA-end values observed in the first month after AA stop. Results: From September 2014, eight pts received first-line AA and, to date, 6 patients (75%) who discontinued the treatment due to PD are evaluable for AWS occurrence. We observed an AWS in 2/6 (33.3%). The first patient, a 76 year-old man, who experienced a PD after 12 wks AA treatment, had a 69% reduction in PSA with PSA dropping from 60 ng/mL to 19.47 ng/mL after about 30 days from the discontinuation. The second patient, 83 years old, treated with AA for 12 weeks, had a reduction in PSA from 112.2 ng/mL to 55 ng/mL at one-month (51% reduction) and to 35.36 ng/mL at two months (68.5% reduction) after AA and PDN discontinuation; after 9 wks the AWS is still ongoing. Conclusions: Notwithstanding the limits of the small sample size, our data shows for the first time that AWS can be observed also in mCRPC patients receiving AA as first-line treatment. Larger observations are needed to establish frequency and clinical role of this phenomenon. Although pathogenetic mechanisms and predictive factors are still unclear, AWS may represent a possibility to delay the second line start for mCRPC pts.
Phase II trial of biweekly reduced-dose combination chemotherapy of oxaliplatin/5-fluorouracil/folic acid (Modified FOLFOX) as first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer
Authors: H. Kim, B. Lee, T. Kim, S. Nam, B. Kim
Journal: Journal of Clinical Oncology (2009)

e15544 Background: Although combination chemotherapy as ECF (epirubicin, cisplatin, and 5-FU) and DCF (docetaxel, cisplatin, and 5-FU) are effective advanced gastric cancer, but it is too toxic to apply for elderly patients with increased comorbidity. Combination of oxaliplatin and 5-FU has proven to be a effective and tolerable regimen in advanced gastric cancer, and we investigated the efficacy and safety of reduced-dose combination chemotherapy of oxaliplatin/5-FU/folic acid as first-line chemotherapy in elderly patients with metastatic or recurrent gastric cancer. Methods: Elderly patients (≥60 years) with measurable, metastatic or recurrent gastric cancer were enrolled. Patients received oxaliplatin 75mg/m 2 (2-hour intravenous infusion on D1), 5-FU 1000mg/m 2 (12-hour continuous infusion on D1,2), and folic acid 20mg/m 2 (15-minute infusion on D1,2) every 2 weeks. Results: Total 37 patients were enrolled between April 2004 and August 2008. Median age was 67 years old (range, 60 to 80 years), and 22 patients (59.5%) had increased Charlson comorbidity index score (CCI ≥1). Of 36 evaluable patients, 2 patients achieved complete response (CR), and 12 patients partial response (PR) with representing overall response rate of 44.4% (95% CI 27.7- 60.2). Stable disease (SD) was observed in 12 patients (33.3%), and progressive disease in 8 patients (22.3%). The median time to progression was 4.6 months, and median overall survival was 9.2 months. Relative dose intensity was 97.4% in both oxaliplatin and 5-FU. Grade 3 or 4 hematologic toxicities included neutropenia in one patients (2.7%), and anemia in three patients (8.1%). Peripheral neuropathy occurred (grade 2) was only observed in three patients (8.1%). Conclusions: The reduced-dose combination chemotherapy of oxaliplatin/5-FU/folic acid was effective and tolerable in elderly patients with metastatic or recurrent gastric cancer as first-line treatment. No significant financial relationships to disclose.
Role of post transplant maintenance therapy in multiple myeloma: Results from a developing country
Authors: M. Sengar, L. Kumar, K. Ganessan, N. Khattry, S. Mohanty, V. Kochupillai
Journal: Journal of Clinical Oncology (2005)

6731 Background: In multiple myeloma, post transplant maintenance therapy has been used to prolong the progression free survival and thus the over all survival. Methods: Seventy patients of multiple myeloma were analyzed to assess the efficacy and tolerability of post transplant maintenance therapy. Results: Seventy patients (52 males, 18 females, median age- 52 years, range26–65 years) were evaluated. Stage IIIA disease was in 70%, remaining were stage IIIB. Pretransplant, 10% were in complete remission, 47% in partial remission and 20% had stable disease. Progressive disease was seen in 23%. Conditioning regimen was high dose melphalan (median- 182 mg/m2, range120- 225mg/m2). Median time for engraftment was 11 days (range 7–24 days). Post transplant, 70% patients achieved complete response, 20% partial response and. 10% failed to engraft. The overall and progression free survival were 65± 0.06%, 40%± 0.07%(median follow up-30 months) respectively. Thirty patients received interferon 2b, 3 MIU twice a week, s.c as maintenance therapy for 1 year (range 6 m - 2.5 years). Ninety five percent patients had fever, fatigue, myalgia and lethargy. No grade \(\frac{3}{4}\) toxicity was seen. The progression free and over all survival were 55±0.1%, 60±0.09%,respectively. 17 patients were randomized to thalidomide (9 patients, 50 mg/d) and interferon (8 patients). Median interval between transplant and the start of maintenance therapy was 3 weeks. The median duration of maintenance was 14 months. All patients except one (interferon arm) remained in complete response till the last follow up. The side effects in thalidomide group were constipation (8), skin rashes (4), peripheral neuropathy (2). In interferon arm fatigue (8), fever (7), myalgia (4) were the main side effects. No grade \(\frac{3}{4}\) toxicity was seen except in one patient who required discontinuation of interferon because of grade 3 myalgia and fatigue. Conclusion: There is a suggestion that post transplant therapy is well tolerated and helps in maintaining remission for a longer period though longer follow up and randomization of larger number of patients is required. No significant financial relationships to disclose.
Reducing the percent of ICU deaths of patients with advanced cancer at Stanford.
Authors: Pelin Cinar, Zarrina Bobokalonova, Eric Hadhazy, Sandy Chan, Holley Stallings
Journal: Journal of Clinical Oncology (2016)

234 Background: Intensive care at the end of life, for patients with advanced cancer can compromise quality of life and result in excessive costs for patients and their families. In 2014, 40% of patients with solid tumors admitted to the Stanford Health Care ICU died with advanced stage disease. Sixty-five percent of the patients with advanced stage saw palliative care (PC) &lt; 7 days of life. The aim was to decrease the percent of advanced solid tumor ICU deaths by 25%, through early palliative care intervention. Methods: The current process was analyzed through mapping and a cause and effect diagram. The outcome measure was defined as percentage of patients with advanced solid tumors dying in ICU. A key intervention was the development of criteria designed to trigger an earlier PC referral for patients with stage III-IV lung/pancreatic cancer. PC referral triggers included: 2+ lines of prior chemotherapy with life expectancy &lt; 6 months or refractory disease, hospitalization within prior 30 days, &gt; 7days of hospitalization, uncontrolled symptoms. ICU trainees were to contact the primary oncologists and discuss the role of PC consultation for patients who met the criteria. A balance measure was developed to assess if primary oncologists were contacted. Charts of patients admitted to the ICU 2 weeks pre- and post-implementation were reviewed. Results: During the pre-PDSA cycle, 13 patients with cancer were admitted to the ICU while 10 were admitted post-PDSA cycle. Primary oncologists of the patients with advanced cancer who met our criteria were contacted in similar rate pre- and post-PDSA (39% vs 40%). PC consultation was also similar for pre- and post-PDSA cycles (31% vs 30%). The percent of ICU deaths of patients in the pre-PDSA was 22% and 22% in the post-PDSA cycles. Conclusions: The percentage of deaths in the ICU for patients with advanced cancer met our target goal of 25% reduction from the baseline. However, the improvement was independent of our intervention, given the timing and short interval. The percent of PC consults for patients meeting the criteria did not change. Data from subsequent PDSA cycles and a SPC chart will be reported in the conference.
Eligibility of metastatic pancreatic adenocarcinoma (MPA) patients for first-line palliative intent nab-paclitaxel plus gemcitabine (NG) versus FOLFIRINOX (FIO).
Authors: Renata D'Alpino Peixoto, Daniel John Renouf, Howard John Lim, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2014)

259 Background: The ACCORD 11 and the MPACT trials recently showed superiority of FIO and NG over gemcitabine alone, respectively. However, both trials had strict inclusion criteria. The aim of this study was to determine the proportion of patients (pts) with MPA who would be potentially eligible for first-line palliative intent chemotherapy with FIO and NG in routine clinical practice. Methods: 473 consecutive pts who presented with MPA and initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the BC Cancer Agency were identified using the provincial pharmacy database. Clinicopathological variables and treatment outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the criteria as described in the respective pivotal phase III trials. Results: In total, median age was 66 years (range 34–89) and 258 (55%) were men. Only 24.7% of the pts would be eligible for FIO as compared to 45.2% for NG. The main reasons for ineligibility for FIO were ECOG performance status (PS) ≥ 2 (56.5%), age &gt; 76 years (19.0%), and bilirubin &gt; 1.5 times the upper limit of the normal range (ULN) (18.6%). The main reasons for ineligibility for NG were bilirubin &gt; ULN (24.5%), ECOG PS ≥ 3 (14.6%), and cardiac dysfunction (13.8%). Median overall survival (OS) for the entire cohort treated with gemcitabine was 5.8 months (95% CI 5.4-6.2). On univariate analyses, eligible pts for FIO had longer median OS than ineligible pts (8.6 vs 4.7 months, p&lt;0.001). Eligible pts for NG also had longer median OS than those deemed ineligible (6.7 vs 4.9 months, p=0.008). After accounting for ECOG PS in the multivariate model, eligibility for either FIO or NG no longered predicted for better OS. Conclusions: In ourpopulation-based analysis, almost twice as many pts would be eligible for NG when compared to FIO, mostly due to ECOG PS. The longer OS observed in the FIO-eligible population likely reflects the exclusion of ECOG PS 2 pts.
Phase II study of weekly docetaxel as salvage therapy for disseminated nasopharyngeal carcinoma
Authors: J. Y. Ngeow, F. Gao, S. S. Leong, W. Lim, C. Toh, E. H. Tan
Journal: Journal of Clinical Oncology (2008)

6057 Background: To evaluate the efficacy and toxicity of single agent docetaxel given as weekly schedule as salvage therapy in patients with disseminated nasopharyngeal carcinoma (NPC). Methods: Patients with histologically confirmed metastatic or recurrent WHO type II/ III NPC who have failed at least one line of palliative treatment but no prior docetaxel were eligible. Only patients with good performance status (ECOG 0–2), adequate reserves and who had measurable metastatic disease were recruited. Patients received weekly docetaxel chemotherapy every 28 days (docetaxel 30 mg/ m2 days 1, 8 and 15), up to a maximum of 6 cycles, until disease progression or the appearance of intolerable toxicity. Patients were evaluated every 2 cycles of treatment for response assessment. QoL assessment (using the EORTC QLQ-C30 ver 3.0) and toxicity were also evaluated. Results: Thirty patients were evaluable for toxicity and response. Patient characteristics were as follows: Median age was 47.7 years (range 25.4–67.8), median number of lines of prior chemotherapy was 2 (range 1–4), the majority of patients had good performance status (ECOG 0–1), and the majority of patients had multiple sites of metastases(83%). Toxicity of grade 3 or more included fatigue in 4 (13%), anemia in 3 (10%) and diarrhea in 1 (3%) patients. The best response outcomes were 11 (37%) partial responses and 4 (13.3%) stable disease. Global quality of life scores were stable during treatment. Using the Kaplan-Meier method, the median progression free survival was 5.3 months and median overall survival of 12.8 months. The partial responders had a mean durable response of 7.9 months (range 5.8 to 11.3 months). Conclusions: Results from this trial suggest that weekly docetaxel is an active salvage agent in patients with disseminated NPC who are refractory to platinum chemotherapy. This is the first study that confirms that docetaxel is an active agent in NPC. No significant financial relationships to disclose.