tbuckley/cabot-search huggingface dataset:
A phase II trial of docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced and metastatic carcinoma of the penis (CRUK/09/001).
Authors: A. K. Bahl, S. Nicholson, J. Barber, E. Hall
Journal: Journal of Clinical Oncology (2010)

TPS240 Background: Chemotherapy for penile cancer is used mainly as palliation of metastatic disease. It also has a role as treatment for locally advanced disease but the rarity of the disease has hampered attempts to define an evidence base for its use. Combined cisplatin (P) and 5-fluororacil (F) has been used for treatment of squamous cell carcinoma (SCC) of the penis since 1990. Pathological similarities to head and neck SCC suggest that addition of docetaxel (T) to an established platinum-based regimen may lead to improved therapeutic benefits. The purpose of the trial is to determine the activity ofTPF chemotherapy in penile cancer Methods: This single stage phase II trial is the only UK-wide trial for penile cancer. Eligible patients (pts) have histologically proven SCC of the penis staged M1; M0, T4 any N; M0, any T, N3 or inoperable N2; or M0, any T, N1 where chemotherapy is to be offered as first-line therapy. Pts must have measurable disease and be fit to receive TPF as palliative or definitive treatment or as treatment for relapse. All pts receive three 21 day cycles of: T 75mg/m2 day 1, P 60mg/m2 day 1, F 750mg/m2/day (days 1-5). Fourteen or more responses in 26 pts are required to conclude a response rate of 60% or more (p0=0.35, p1=0.60, α=0.1, β=0.2; Fleming-A'Hern exact methods). The primary endpoint is overall response rate (RECIST) assessed by MRI/CT scan at completion/discontinuation of trial treatment. The proportion of pts with inoperable locoregional disease rendered operable following TPF, safety, tolerability, and progression-free and overall survival are secondary endpoints. The trial opened in September 2009. To end 2009, 4 pts have been recruited of which two have completed trial treatment and remain on follow-up. The National Cancer Research Institute's Penile Cancer Studies Group plans further studies. If results suggest a high response rate, they are likely to lead to an expanded phase II TPF programme in two settings: as neoadjuvant therapy (in operable and inoperable disease); and as palliation of metastatic disease. The trial also takes the first steps to defining a standard of care for synchronous chemoradiotherapy as consolidation for inoperable locoregional disease. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Pfizer, Roche, sanofi-aventis sanofi-aventis
A phase I/II study of a HER2/neu (HER2) peptide vaccine plus concurrent trastuzumab
Authors: D. J. Webster, J. Waisman, B. Macleod, C. Dela Rosa, D. Higgins, P. Fintak, J. Childs, M. Slota, L. G. Salazar, M. L. Disis
Journal: Journal of Clinical Oncology (2006)

2528 Background: HER2 is a tumor antigen in breast and ovarian cancer. Vaccines targeting both Class I and II epitopes of HER2 can elicit long-lived cellular immunity. Trastuzumab increases the activity of HER2-specific T cells in vitro. This study examines the safety and immunogenicity of a HER2 peptide vaccine given with trastuzumab to augment HER2-specific immune responses in vivo. Methods: 20 HLA-A2+ subjects will be enrolled on this Phase I/II single institution trial. Eligible subjects must have stage IV HER2 overexpressing breast or ovarian cancer, stable or no evident disease on maintenance trastuzumab and a normal baseline MUGA. Subjects must have ECOG performance status 0–1, creat ≤ 2.0, bili &lt; 1.5 × ULN, SGOT &lt; 2 × ULN. The HER2 vaccine used in this study has been previously reported and is composed of 3 HER2 Class II epitopes encompassing Class I epitopes in their natural sequence. (Knutson et al, J Clin Investigation 107:477–484, 2001). Subjects receive 6 vaccinations + GM-CSF at monthly intervals. Primary endpoints are safety and immunogenicity. Results: To date, 14 of 20 subjects have been enrolled. A total of 77 vaccinations have been given. Of 276 reported toxicities, 88% were Grade 1; most common were constitutional symptoms (25%), injection site reactions (14%), and cytopenias (14%). 11% of toxicities were Grade 2; most common were lymphopenia (34%) and headache (19%). There was one Grade 3 toxicity (syncope 5 hours after vaccination) and one Grade 4 toxicity (stroke secondary to brain metastases in long-term follow up). Cardiac toxicity included two Grade 2 asymptomatic decreases in LVEF (54 to 49% and 64 to 45%.) The average decrease in LVEF between baseline and 9 month post-vaccine follow up was 5% ± 5.85 (n = 10). Of the 10 patients who have had immunologic analysis performed at multiple time points, 5 have developed significant T cell immunity to either HER2 overlapping peptide pools and/or HER2 peptides. Complete immunologic analysis will be presented. Conclusions: Subjects with HER2 overexpressing Stage IV cancer can be safely immunized with a HER2 peptide vaccine while receiving concurrent trastuzumab without additional cardiac toxicity. In addition, the approach is immunogenic, generating significant levels of HER2-specific T cells in the peripheral blood. No significant financial relationships to disclose.
Prospective Evaluation Of Risk Factors For Clostridium Difficile Colonization Among Allogenic Hematopoietic Stem Cell Transplant Recipients, 2010-2012
Authors: Tania Jain, Christopher Croswell, Harsha Vardhan Reddy Banavasi, Varinia Urday-Cornejo, Alyssa Liubakka, Jessica Cutright, Hossein Salimnia, Paul Lephart, Sanjay Revankar, Pranatharthi Chandrasekar, Teena Chopra, Abhinav Deol, George Alangaden
Journal: Blood (2013)
A phase II trial of 13-cis retinoic acid, interferon, docetaxel, and estramustine (RITE) for the treatment of hormone refractory prostate cancer (HRPC)
Authors: A. Mehta, M. N. Stein, S. Goodin, S. Doyle-Lindrud, M. Todd, E. Rubin, E. White, C. Jeyamohan, D. Metzger, R. S. DiPaola
Journal: Journal of Clinical Oncology (2007)

15542 Background: Efficacy of chemotherapy for the treatment of HRPC is limited secondary to the development of multiple mechanisms of resistance. In our prior studies, we demonstrated the safety and activity of docetaxel (T) 40 mg/m2 given with 13-cis retinoic acid (R), interferon alpha (I) and estramustine (E), along with a decrease in the expression of the anti-apoptotic protein Bcl-2. To test whether this regimen had clinical activity in HRPC, we conducted a phase II trial with the combination of these drugs. Methods: Eligible patients (pts) received 13-cis retinoic acid 1 mg/kg on days 1 to 4, interferon alfa 6 million units/m2 on days 1 to 4, estramustine 280 mg three times a day on days 1 to 5, and docetaxel 40 mg/m2 on day 2, all repeated every 21 days. Pts had peripheral blood mononuclear cells (PBMCs) obtained prior to therapy and on days 2 through 4 of the first cycle to assess the effect of therapy on the expression of Bcl-2. Results: Nineteen of 20 registered pts (mean age 66) have been treated in this trial. The median pre-treatment PSA was 33.3 ng/mL. A PSA decrease was seen in 13/19 pts (68%) with a mean decrease of 50.3%. A PSA decrease ≥ 50% was seen in 7/19 pts (37%), with an average PSA decrease of 70.4% in these pts. One patient had an objective response (partial remission). The median time to progression (TTP) was 16.3 weeks (range: 3.1 - 132.6 weeks). Three pts remain on study with a median TTP of 25.1 weeks (range: 6.1 - 132.6 weeks). Grade 3 toxicities included 2 pts with hypophosphatemia, 1 patient with neutropenia, and 1 patient with flu-like symptoms. One patient experienced a pulmonary embolism and one patient had a portal vein thrombosis. Common Grade 2 toxicities included fatigue (21%), cytopenias (21%) and GI side effects (16%). There was no treatment-related mortality. Conclusions: These data support the efficacy of the RITE regimen, and the possibility of using alternative Bcl-2 modulating agents in combination with docetaxel in future studies. In addition, long term treatment with low dose docetaxel may be feasible. The assessment of an effect on PBMC Bcl-2 expression is ongoing. No significant financial relationships to disclose.
Capecitabine in advanced breast cancer: Predictive factors for response
Authors: M. Siva, P. Correa, S. Skaria, P. Canney
Journal: Journal of Clinical Oncology (2008)

1126 Background: Capecitabine is increasingly used in the treatment of metastatic breast cancer (MBC). We evaluated the use of capecitabine therapy (XT) in MBC at our centre, to determine factors that might predict response. Methods: We reviewed the records of patients (pts) with MBC who received XT, from February 05 to March 06. The duration of XT, whether use was continuous or intermittent, the line of use and concurrent treatments were evaluated. Response to XT was correlated to potential predicitve factors including age, tumour grade, estrogen receptor (ER) status and HER2 expression. Time to progression (TTP) and overall survival (OS) after XT were calculated. Results: Seventy-two women received XT with a median age at initiation of 57 years. At diagnosis, 44% had grade 3 tumors. ER was positive in 61% and HER2 over-expressed in 33%. Adjuvant chemotherapy was given to 61% and adjuvant hormones to 54%. Median time to first relapse was 29 months (mths). XT was used commonly as 2nd- (26.4%) or 3rd-line (30.6%) treatment after relapse. XT was continuous in 83% and intermittent in 17%. Median number of XT cycles was 4 (range: 1–37). An objective response was noted in 23% and the overall clinical benefit rate was 43% (partial/good responses plus stable disease). The only positive correlation to predict response was ER positivity (p = 0.04). Common significant toxicity included grade 2, palmo-plantar erythema (22%) and fatigue (15%). In 22% a dose modification or delay was necessary. XT was stopped in 5 pts due to toxicity. Median OS after XT was 12 mths (95% CI 6.87–17.13) and median TTP on XT 3 mths (95% CI 2.07–3.93). Conclusions: XT remains an important palliative treatment option for patients with MBC. Patients with ER positive tumours respond better to XT. We did not identify any other factor that predicted response to XT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Roche Roche Roche
Non-Hodgkin’s lymphoma patients at a VA medical center: Co-morbidity and its impact on survival
Authors: M. Cholankeril, S. Srinivas, V. T. Chang, K. Demissie, M. L. Gonzalez, F. Zhong, B. Crump, M. McPherson, J. Einhorn, B. S. Kasimis
Journal: Journal of Clinical Oncology (2008)

19502 Background: To determine whether three co-morbidity indices, the Charlson Comorbidity Index (CMI), the Kaplan- Feinstein Comorbidity Index (KFI), and the Cumulative Illness Rating Scale (CIRS) predict survival in lymphoma pts. Methods: In an IRB approved study, we reviewed records with NHL at the VANJHCS from 1/1/1997 through 12/31/2007. Results: There were 98 pts with 59 deaths (60%).The median (M) age was 62 years (27–89). The overall M survival (MS) was 702 days (6–3976) and M Hemoglobin (HgB) was 12.3gm.dl (7.3–17.4). The M LDH was 198 IU/dl (86–1905), M Albumin was 3.8g/dl (1.2–5.4), M ECOG PS was 1(0–4) in 47 pts (47%). Histological categories were Low Grade 52 pts (53.6%), Intermediate (IGL) 35 pts (36.1%) and Mantle Cell Lymphoma(MCL) 10 pts (10.3%). M survival in LGL was 1084 days (6–3976), IGL was 484 days (17–3402), and MCL was 574 days (62–1415). The CMI, CIRS, and KFI were tabulated for 98 pts. The Follicular Lymphoma International Prognostic Index (FLIPI) score, as well as the IPI (International Prognostic Index) were calculated. The M CMI was 6(1–12), M KFI was 3(1–3), M CIRS15 4(1–9), M CIRS16 8(2–14), M CIRS17 1.7(1–3.3), M CIRS 18 0(0–4). Both univariate and multivariate Cox regression survival analyses were performed with SAS. In patients with LGL, univariate survival predictors were CIRS 18, KFI and LDH. In multivariate analyses survival predictors were albumin (p<0.0.024), FLIPI(p<0.04), and CIRS 17(p<0.05). Univariate analyses in IGL showed KFI (p<0.053), CIRS 16(p<0.065) and IPI (p<0.028) predict survival. Independent predictors in multivariate analyses includes IPI(p<0.006), CIRS16(p<0.055), CIRS 17(p<0.075) and Hgb(p<0.05). Conclusions: This data provides evidence for co-morbidity as an independent predictor of survival in pts with LGL and IGL. Further work in larger groups of pts is warranted. If confirmed it can be a useful tool for better selection of pts for clinical trials. No significant financial relationships to disclose.
Synergistic antitumor activity of the SN-38-incorporating polymeric micelles NK012 with S-1.
Authors: T. Nagano, M. Yasunaga, K. Goto, H. Kenmotsu, Y. Koga, J. Kuroda, Y. Nishimura, T. Sugino, Y. Nishiwaki, Y. Matsumura
Journal: Journal of Clinical Oncology (2010)

e13588 Background: The combination therapy of CPT-11, a prodrug of SN-38, with S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, shows a high clinical response rate in non-small cell lung cancer (NSCLC). However, this combination causes severe toxicities such as diarrhea. Here, we investigated the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with S-1 in female BALB/c nude mice bearing a NSCLC xenograft in terms of antitumor activity and toxic effects, particularly intestinal toxicity. Methods: In vitro cytotoxic effects were examined in human NSCLC cell lines (A549, PC-9, PC-14, EBC-1, and H520). In vivo antitumor effects were evaluated in PC-14- and EBC-1-bearing mice after NK012 or CPT- 11 intravenously administration on days 0 and 7 and S-1 administration by oral gavage once a day on days 0 to 13. Pathological changes in the small intestine were also investigated. Results: The in vitro growth inhibitory effects of NK012 were 56.8- to 622-fold more potent than those of CPT-11. NK012/S-1 treatment showed significantly higher antitumor activity both in PC-14-bearing (p=0.0007) and EBC-1-bearing mice (p<0.0001) than CPT-11/S-1 treatment. The deformity and decrease in the density of intestinal villi were more severe in CPT-11/S-1-treated mice than in NK012/S-1-treated mice. Conclusions: NK012/S-1 combination is a promising candidate regimen against NSCLC without inducing toxicities such as severe diarrhea and therefore warrants clinical evaluation. No significant financial relationships to disclose.
The role of age and race in receiving breast cancer treatment: A cross-sectional survey of an urban population
Authors: A. Naeim, R. C. Maly
Journal: Journal of Clinical Oncology (2005)

6047 Background: Breast cancer treatment differences in older patients and in certain groups. These differences may be due to a variety of factors, in addition to age and race, which include: comorbid illnesses, performance status, socioeconomic status, and education. Methods: The sample consisted of a cross-sectional survey of 257 Latina, African American and White women living in Los Angeles County, age 55 or older from the Los Angeles County Cancer Surveillance Program’s (CSP) rapid ascertainment program (the Tumor Registry) who were between three and nine months of diagnosis and at least one month post treatment. These patients were interviewed, their medical records abstracted, and the doctor’s surveyed. The primary outcomes for this analysis were surgical, radiation, hormone, and chemotherapy treatment options. Logistic regression analysis was used controlling for age, race/ethnicity, socio-demographic characteristics, Katz comorbidity, functional status, and stage of disease. Results: Univariate analysis demonstrated significant trends with age and race across most treatment choices. In multivariate analysis, the effect of age and race was less pronounced. Factors such as insurance status, comorbidity, and education were very significant for treatment selection. Medi-Cal patients were less likely to receive lumpectomy (Odds Ratio, OR=0.19) and none received reconstruction post mastectomy. Educated patients were more likely to have an axillary lymph node dissection, LND, (OR=7.5) and post-lumpectomy radiation (OR=3.94). Those with higher Katz comorbidity were less likely to receive a LND (OR=0.70) or chemotherapy (OR=0.76). Nevertheless, older women were less likely to have LND (OR=0.49) and chemotherapy (OR=0.24) compared to younger women. African-American women were less likely to have adjuvant hormone therapy (OR=0.50) compared to Caucasians and Latinas. Conclusion: Although age and race are factors in certain breast cancer treatment decisions, other factors such as education and insurance status and may serve as important targets in order to improve care. No significant financial relationships to disclose.
Randomized phase III trial of 2<sup>nd</sup> line gemcitabine/paclitaxel chemotherapy in patients with advanced bladder cancer: Temporary versus maintenance treatment (German Association of Urologic Oncology (AUO) Trial AB 20/99)
Authors: P. Albers, R. Siener, S. Park, G. Fechner, U. Steiner, J. Lehmann, D. Heimbach, A. Heidenreich, R. Fimmers
Journal: Journal of Clinical Oncology (2008)

5030 Background: In a recent randomized phase II trial, the 2nd line combination of gemcitabine (G) and paclitaxel (P) had achieved a 44% overall response (OR) rate (ASCO 2002, #797). Based on these results, aim of this phase III trial was to show an advantage of a maintenance treatment instead of 6 cycles G/P and to analyse prognostic factors of response to treatment. Methods: From 11/2001 to 11/2005, 102 patients were randomized to receive either 6 cycles (group A) or a maintenance treatment until progression (group B) of 3-wkly G (1000 mg/qm, d1+8) and P (175 mg/qm, d1). Response was measured according to RECIST. All patients had previously been treated with a cisplatin-based regimen. The trial was powered (90%, alpha 5%) to show at least a 9.1 months difference in disease-specific survival (DSS) in favour of the maintenance treatment. Results: As of today, 9 patients are still alive. After intention-to-treat analysis, median overall survival (OS) was not significantly different with 7.5 ms (0.4–48.8) and 6.8 ms (0–40.7) in group A and B, respectively (log-rank p=0.8029). Fifty-seven patients were evaluable for response (group A: 29, group B: 28; all patients with > 2 cycles) with a mean number of 4.6 and 5.6 cycles in group A and B, resp. Median PFS and OS was 4.5 and 7.8 ms in group A and 3.3 and 7.4 ms in group B, resp (log-rank p=0.5554 and p=0.3595). The overall response rate with 34.5% in group A and 50.0% in group B was not significantly different. Pts with major response to 1st line treatment tended to respond again to 2nd line treatment (p=0.058) and pts with a median duration of response to 1st line treatment of 7.1 ms [95% CI 2.0; 12.2] had a significantly better response to 2nd line treatment than pts with a median duration of response of only 2.9 ms [95% CI 0.9; 4.8] (p = 0.0157). Treatment was well tolerated with only one toxic death in group B. Conclusions: This trial confirms previous phase II data of an up to 50% overall response rate after G/P 2nd line chemotherapy. However, overall and DSS cannot be prolonged by maintenance treatment. Patients with major and durable response to 1st line treatment benefit most from 2nd line chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology Bristol-Myers Squibb, Lilly Oncology
Modified FOLFOX in combination with docetaxel for patients with metastatic adenocarcinoma of the stomach or gastroesophageal junction: A multicenter phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)
Authors: S. Al-Batran, J. T. Hartmann, R. Hofheinz, R. Mahlberg, N. Homann, S. Probst, J. Stoehlmacher, M. Fritz, V. Rethwisch, G. Seipelt, E. Jäger
Journal: Journal of Clinical Oncology (2007)

4545 Background: The combination of docetaxel, cisplatin, and fluorouracil (DCF) is clearly superior to CF in the treatment of patients (pts) with advanced gastric cancer (AGC). DCF is, however, associated with significant toxicity, including neutropenia, febrile neutropenia, diarrhea and mucositis. This study evaluated a biweekly, oxaliplatin-based modification of DCF. Methods: Pts with measurable, locally advanced or metastatic adenocarcinoma of the stomach or GE-junction and no prior chemotherapy received mFOLFOX (oxaliplatin 85 mg/sqm, leucovorin 200 mg/sqm, and fluorouracil 2.6 g/sqm via 24hr infusion) in combination with docetaxel 50 mg/sqm on day 1 every 2 weeks (FLOT-regimen). Prophylactic G-CSF was not administered. Overall response rate (RR) was the primary endpoint (power 80% to detect a RR of &gt;40%) and toxicity profile the main secondary endpoint. The study was externally monitored according to GCP and data were reviewed by an independent safety board. Results: 59 pts (male, 41; female, 18) were enrolled. At the time of analysis, 53 pts were evaluable for toxicity and 51 pts for response. Median age was 60 (range, 29–76), median ECOG PS was 1, and almost all (93%) pts had metastatic disease. Of 51 pts, 2 had a CR and 25 pts attained a PR, adding to an overall RR of 53% (ITT-analysis). Stable disease was observed in 12 (23.5%) and progressive disease in 6 (11.8%) pts. Six (11.8%) pts were not evaluable for response. NCI-CTC grade 3 or 4 hematologic toxicity included leukopenia in 12 (22.6%), neutropenia in 23 (43%), and anemia in 2 (3.8%) pts. Febrile neutropenia was observed in 1 (1.9%) pt only. Other grade 3 or 4 toxicities included peripheral neuropathy in 4 (7.5%), nausea in 3 (5.7%), vomiting in 2 (3.8%) as well as diarrhea and fatigue in 5 (9.4%) pts each. No treatment related deaths were observed. Conclusions: FLOT is active and has a favorable toxicity profile in the treatment of pts with AGC. It may show activity also in perioperative treatment settings and may be considered as a useful treatment option for elderly pts. Survival data will be presented at the meeting. [Table: see text]