tbuckley/cabot-search huggingface dataset:
Phase I/II study of a 3 weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive (HER2+) early stage breast cancer (ESBC) patients (pt). GEICAM 2003–03 study
Authors: A. Antón, A. Ruiz, M. A. Seguí, L. Calvo, M. Muñoz, J. Lao, C. Vázquez, L. Fernández
Journal: Journal of Clinical Oncology (2007)

11032 Background: The liposome-encapsulated form of doxorubicin (Myocet™) (M) seems to be safe in terms of cardiotoxicity in combination with standard doses of trastuzumab (H) and paclitaxel in BC. This phase I/II study of M, H, docetaxel (T) and pegfligrastrim (N) was designed to evaluate the efficacy and safety of the combination, and define the MTD, in order to examine the selected regimen in a phase II trial. Methods: Cohorts of 3 HER2+ (FISH+) ESBC pt were treated at fixed dose of N (6 mg) and H (2 mg/kg/week). M and T were administered at the following dose levels (DL) (mg/m 2 ): DL0, 60/75; DL-1, 55/75; DL-2, 50/70; DL-3, 50/65; DL-4, 50/60. The MTD was defined as &gt;1/6 pt in any cohort experiencing a predefined dose-limiting toxicity (DLT) in cycle (cy) 1 or 2. LVEF was assessed at baseline and every 2 cy. Results: Nineteen pt have been enrolled in phase I; all are evaluable for efficacy and toxicity. Median age was 45. Twelve pt (63%) were premenopausal. Median tumour size was 45 mm (20–80); 13 (68%) and 6 pt (32%) presented with stage II and IIIA BC respectively. Six (32%) of tumours were G3. DLT were G3 diarrhoea, febrile neutropenia, thrombocytopenia, infection, and G4 asthenia. Three additional pt were treated at DL-4 for confirmation of the recommended dose; none of them had a DLT. One pt (DL-2) experienced asymptomatic, reversible LVEF decrease to 49%. All pt have been assessed for pathological response: 6 (32%) and 5 pt (26%) achieved one pCR and one pPR in breast, defined as Miller and Payne score of 5 and 4, respectively. Conclusions: Concomitant administration of M plus THN is highly active regimen with manageable toxicity in pt with HER2+ ESBC tumours. DL-4 has been selected as the DL for the ongoing phase II study with an enrolment target of 59 pt. No significant financial relationships to disclose.
FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer: Results of a phase II trial and role of PET-CT as early predictor of reponse.
Authors: F. Bertolini, N. Malavasi, L. Scarabelli, G. E. Gerunda, G. Colucci, A. Fontana, R. Depenni, S. Zironi, G. Luppi, P. F. Conte
Journal: Journal of Clinical Oncology (2010)

e14108 Background: In patients (pts) with colorectal liver metastases (CLM) R0 resections significantly improve OS. In this report we present the results of a phase II trial with FOLFOX6-BV as neo-adjuvant therapy for pts with non optimally resectable CLM. Methods: Pts with initially unresectable CLM with regard to number, size or locoregional invasionand no evidence of extra-hepatic disease, received FOLFOX6 for 6 cycles (cy) and bevacizumab (BV) 5 mg/kg, every 2 weeks for 5 cy. Pts who did not reach the resectability after the first 6 cy were submitted to other 6 cy of chemotherapy and 5 of BV, then to a new surgical evaluation. CLM were initially documented by biopsy and a CT scan; moreover a PET-CT performed at baseline, within 1 month from the start of preoperative therapy and before surgery. Elective surgery was planned at least 6 weeks after the last dose of BV and 4 weeks after last dose of FOLFOX6. Results: From September 2005 and July 2009, 21 pts were enrolled (male/female: 15/6; median age: 65 years, range: 37-72 years). After 3 months of treatment 12 pts (57.1%) experienced an objective response (CR: 3, PR: 9) documented by RECIST criteria. Among CRs, one pt achieved a radiological CR, but died for toxicity (sepsis) before surgery. Thirteen pts underwent radical surgery (61.9%) and in 3 cases we documented a pCR (23%). One pt was evaluated as in SD by RECIST criteria, but the resected lesion showed the absence of neoplastic cells. Twelve pts were operated after 6 cy and 1 pt was operated after 12 cy. Six pts (46.1%) experienced minor postsurgical complications: 3 had abdominal abscess and 3 a delay in wound healing. After a median follow-up of 38.8 months, median OS was 22.5 months (range: 4-42 months). Pts achieving a reduction in the SUVmax of at least 1 unit between the first and the second PET-CT have a longer PFS (mPFS: 22 vs. 14 months, p = 0.0010). Conclusions: FOLFOX6-BV is feasible and does not increase postsurgical complications. The combination leads to a high resectability rate and increases the number of pts achieving a complete pathologic response. Early changes in PET-TC in particular in terms of reduction of SUVmax seem to be a predictor of longer PFS. No significant financial relationships to disclose.
Seventy percent of complete responders remain in continuous remission: Five-year follow-up of 300 patients treated with fludarabine, cyclophosphamide, and rituximab (FCR) as initial therapy of CLL
Authors: C. S. Tam, S. O'Brien, W. Wierda, S. Lerner, H. Kantarjian, M. J. Keating
Journal: Journal of Clinical Oncology (2007)

7008 Background: The early results of 224 CLL patients receiving the FCR regimen were previously reported (JCO 23:4079). Mature follow-up data (median 62 months for survivors) is now available for the complete cohort of 300 patients. Methods: Eligible patients were =16 years old with previously untreated CLL requiring therapy. Median age was 57 years (31%=60 years, 14% =70 years), and 61% &amp; 36% were in modified Rai intermediate &amp; high risk categories respectively. Prognostic factors: B2m &gt;2x normal 42% (n=295), CD38 positive 28% (n=253), abnormal metaphase cytogenetics 29% (n=221), IgVH unmutated 66% (n=94), ZAP-70 positive 49% (n=88). The planned six cycles of therapy were completed in 74% patients. Results: Responses were: 72% CR, 11% nodular PR (PRn) &amp; 12% PR. On multivariate analysis, CR rates were inferior in patients with B2m &gt;2N (p=0.001) and white cell count &gt;150 × 109/L (p=0.01). Rai stage, CD38 positivity, IGVH mutational status and ZAP-70 positivity were not associated with inferior CR. Median Times to Progression (TTP) were 80 months for CR (n=216), 80 months for PRn (n=32) &amp; 27 months for PR (n=36), with 77%, 65% and 28% projected to be progression-free at five years; projected 5 yr survival were 90%, 81% and 37% respectively. Restricting the analysis to 190 patients with at least five years followup, actual 5 yr TTP and 5yr survival were 70% &amp; 88% respectively in complete responders. Five cases of Richter transformation and eight cases of MDS/AML occurred during remission, with projected 5 yr risk of 2% &amp; 3% respectively. When compared with a historical cohort of patients receiving fludarabine (n=190) or fludarabine and cyclophosphamide/mitoxantrone (n=140) in multivariate analysis, FCR was independently associated with superior TTP (p&lt;0.001) and survival (p&lt;0.001). Conclusion: FCR is the most effective CLL frontline regimen reported to date. 70% of complete responders remain progression-free at five years. No significant financial relationships to disclose.
GEP01: A phase I study of lapatinib (L) and vinorelbine (VNR) in HER2 overexpressing (HER2+) locally advanced or metastatic breast cancer (LAMBC) patients (pts): A FNCLCC Group of early phase trials study
Authors: E. Brain, F. Dalenc, F. Lokiec, V. Dieras, J. Bonneterre, K. Rezaï, F. Mefti-Lacheraf, H. Roché, M. Jimenez, P. Fumoleau
Journal: Journal of Clinical Oncology (2009)

1051 Background: Lapatinib is an effective anti-HER-2 therapy in LAMBC pts, currently investigated in the adjuvant setting. Following anthracyclines, taxanes and capecitabine, VNR is an active agent in metastatic setting. Its main toxicity consists of neutropenia and may challenge the standard weekly, day D1 and D8 regimen. We investigated the combination of L + VNR, seeking the recommended dose for further phase II studies and the potential pharmacokinetic (PK) interactions. Methods: Women with a HER-2+ LAMBC, in progression after ≤ 2 lines of trastuzumab-based treatment were treated with a 7D (D-7 to D0) loading dose of L before starting VNR on a D1 and D8 q3w IV regimen. L was given orally continuously. Primary prophylaxis of febrile neutropenia (FN) with G-CSF was not permitted. Dose levels (DL, L [mg]/VNR [mg/m 2 ]) ranged from 750/20 to 1250/30 with 3 pts/DL (6 in case of dose-limiting toxicity [DLT]). DLT was defined on tolerance at cycle 1 and included grade (gr) 4 neutropenia (PN) ≥ 7D, FN, thrombocytopenia (gr4 or symptomatic gr3), omission of D8 for haematological toxicity, and any drug-related gr3–4 non-haematological toxicity. PK samples were collected on 7 points on D1 of cycle 1 for L and VNR dosages. Results: From August 2007 to December 2008, 15 evaluable pts were enrolled (median age 58 [46–75], 43% PS 0, 8 pts previously exposed to only 1 line of trastuzumab) and 65 cycles were administered. Toxicity is available for 13 pts. Of 3 pts treated at DL4 (1000/25), 2 developed a DLT: 1 FN and 1 gr4 PN &gt; 7D. Other significant toxicities (% pts) included gr2 anaemia 8%, gr4 PN 46%, gr1 diarrhoea 62%, gr2 nausea/vomiting 8%, gr1 skin rash 23%, gr2 transaminases 23%; no decrease of cardiac function occurred. From DL1 to DL3 (750/20, 1000/22.5), total body clearance of VNR decreased by 50% (32 ± 19 L/h vs 17 ± 7 L/h). Conclusions: Maximal tolerated dose has been reached at 1000/22.5 for the combination of L with VNR given on a D1 and D8 q3w schedule. Given a potential PK interference which would yield to higher exposure to VNR, an intermediate DL is going to be explored (1250/22.5) to allow an accurate definition of the recommanded dose of the combination for future phase II comparison studies. [Table: see text]
Phase II study of capecitabine (C) in combination with docetaxel (D) as neoadjuvant treatment in patients with locally advanced breast cancer (IIIA and IIIB stage). Correlation between clinico-pathological response and fluoropyrimidine-enzyme profile. Early results
Authors: M. Bellet, M. Muñoz, M. Suárez, J. Corominas, B. Bellosillo, T. Maristany, J. Perich, I. Tusquets, X. Fabregat
Journal: Journal of Clinical Oncology (2005)

735 Background: Capecitabine (C) and Docetaxel (D) have demonstrated synergy in preclinical studies and efficacy in metastatic breast cancer. Our primary objectives were to determine the clinical and pathological response/toxicity of neoadjuvant QT with C and D. Expression levels (mRNA) of 3 enzymes involved in C and 5-FU intratumoral activation and metabolism thymidylate synthase (TS), thymidine phosphorilase (TP) and dihydropyrimidine dehydrogenase (DPD) were determined in tumoral biopsies before treatment. Its relationship with clinical and pathological response was analyzed Methods: : Pts with IIIA/ IIIB, adequate organ functions and KPS 80 were 1st treated with 4 cycles of C: 1250 mg/m2 (1000 mg/m2 for age>60) bid, d.1–14 and D: 75 mg/m2 on day 1 in a 3-weekly followed by surgery, adjuvant AC every 3 weeks x 4 ± tamoxifen according to ER and PR status Results: 32 pts with LABC IIIA/IIIB: 15(47%)/17(53%) have been enrolled. Age 52 y (30–72). KPS 90% and tumor size 6.8cm (2–20). N1:41%,N2/3:37.5%, ER and PR-/p53+/Her-2+: 25%/24%/28%.A total of 114 cycles of C and D were administered (median 4, range 1–4). Tox: Neutrop. G3/G4: 72% and F.Neutrop:15.6%. AE G3/G4,were HFS 28%, diarrhea 16%, asthenia 9% and stomatitis 6%. There were no toxic deaths. Efficacy: 2 pts were prematurely withdrawn due to AE and 1 pt was not evaluable for response. 29 pts were evaluable for CR: 5 CR (17%); 18 PR (62%), 6 EE (21%). 24 pts were evaluable for pCR: 3 pCR (12.5%), 9 (37.5%) had ≤ 10mm residual tumor (3 microscopical RD) in breast. Median afected nodes: 3. High TP/DPD ratio was associated with CR(p 0.037) and both high TP/DPD and low TS/DPD ratio correlate with residual tumor ≤1 cm in breast (p=0.035). Conclusions: Neoadjuvant combination of C and D appears to be a regimen with substantial clinical activity.Toxicity profile was similar to that reported in anthracycline-pretreated population with less stomatitis. A high TP/DPD ratio correlates with clinical response and a favourable enzymatic profile (high TP/DPD and low TS/DPD ratio) may predict for a good pathological response. No significant financial relationships to disclose.
Evaluating the impact of relative total dose intensity (RTDI) on patient's short- and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer: A pooled analysis
Authors: S. Loibl, V. Nekljudova, T. Skacel, M. Schwenkglenks, H. Lück, T. Brodowicz, C. Zielinski, G. von Minckwitz
Journal: Journal of Clinical Oncology (2009)

1065 Background: The consequences of reducing chemotherapy dose intensity might be extensive, potentially affecting short- and long-term outcomes as well as patient quality of life, the dose and schedule are of central concern in the delivery of chemotherapy. Methods: This statistical analysis was based on individual subject data of 934 patients (pts) obtained from the following prospective, open-label, randomised phase III trials in metastatic breast cancer that recruited between 1996 and 2005 investigating an anthracycline/taxane based first-line chemotherapy: CECOG trial, AGO-Mamma-1 and AGO-Mamma-3 trial. The primary objective of the analysis was to evaluate the influence of RTDI on progression free survival (PFS) in different predefined binary RTDI cuts from 75% to 95% with an interval at every 5%. Relative total dose intensity (RTDI) is the ratio of actual total dose intensity and planned total dose intensity, expressed as a percentage. RTDI quantifies dose reductions and delays, as well as premature discontinuations in treatment. Results: Overall cuts pts with higher RTDI had a shorter PFS compared to those with lower RTDI. A time dependent term for low RTDI was included in the analysis and showed the opposite effect after approximately 60 weeks. The overall median PFS was 39 weeks. Analysis of the Kaplan-Meier curve identified many early events in patients with high RTDI. We hypothesized that patients with a primary progression (PP) who have by definition a high RTDI were responsible for this effect. The PFS excluding 114 patients with PP showed no difference for patients with high compared to those with low RTDI. The median overall survival (OS) for the whole study population was 98 weeks. Excluding patients with PP, the median OS was 118 weeks (95% CI [103–136]) for those with RTDI ≥ 85% versus 96 weeks (95% CI [83–119]) if RTDI was &lt; 85% (log-rank p = 0.0086). The results were comparable across other cut levels. Conclusions: Maintaining RTDI in patients not experiencing PP might have significant impact on overall survival. No significant financial relationships to disclose.
Mammographically occult contralateral breast carcinoma detected by magnetic resonance imaging in the elderly
Authors: J. R. Bernard, L. A. Vallow, E. R. DePeri, D. G. Feigel, S. Amar, S. J. Buskirk, E. A. Perez
Journal: Journal of Clinical Oncology (2008)

500 Background: Magnetic resonance imaging (MRI) may be able to detect clinically and mammographically occult contralateral breast carcinoma in 3.1% of newly diagnosed breast cancer patients (Lehman CD, et al. N Engl J Med 2007;356:1295–303). Breast cancer incidence has been shown to have a strong correlation with patient age. The incidence of mammographically occult contralateral breast cancer detected by MRI in women with newly diagnosed breast carcinoma in patients > 70 was assessed at our institution. Methods: Between 7/2003 and 07/2007, 159 women age > 70 with pathologically confirmed, newly diagnosed breast cancer were identified from an IRB approved MRI database. Patients noted to have a synchronous contralateral abnormality identified by MRI, but not evident on mammography or clinical examination, were reviewed. Those patients in which biopsy was recommended and performed were further analyzed to determine the incidence of pathologically diagnosed contralateral carcinoma. Results: The median age at diagnosis was 75 (range = 70–91). Mammographically occult contralateral breast abnormalities were described in 65 (41%). Of those women with a contralateral abnormality, biopsy was performed in 28 (43%). Of the women who underwent a biopsy, 9 (32%) had pathologically confirmed carcinoma, whereas 19 (68%) women had other benign diagnoses. Five patients were found to have invasive carcinoma and 4 patients were diagnosed with ductal carcinoma in situ. The overall incidence of mammographically occult contralateral carcinoma in our elderly patient population was 5.7% (9/159). The sensitivity, specificity, positive predictive value, and negative predictive value of MRI were 100%, 87%, 32%, and 100%, respectively. Conclusions: The Mayo Clinic Jacksonville experience suggests that up to 5.7% of newly diagnosed elderly breast cancer patients may have a clinically and mammographically occult carcinoma detected by MRI. Older age should not be a deterrent to obtaining breast MRI and in fact, because of the higher tendency to have a contralateral carcinoma, should be considered. Further study in the use of MRI for screening in this population is needed for corroboration. No significant financial relationships to disclose.
Correlation between bevacizumab-related hypertension and response in mCRC patients.
Authors: A. De Stefano, L. Cannella, C. Carlomagno, A. Crispo, R. Bianco, R. Marciano, S. Pepe, S. De Placido
Journal: Journal of Clinical Oncology (2010)

3581 Background: Patients (pts) with metastatic colorectal cancer (mCRC) receiving all active drugs (irinotecan, oxaliplatin, fluorouracil) achieve the best outcome. Bevacizumab (Bev) increases progression-free (PFS) and overall survival when added to chemotherapy (ChT). Arterial hypertension (aHT) has been reported in all trials involving Bev. We hypothesized that Bev-induced aHT may be a potential predictive marker of response to treatment with ChT + Bev, and retrospectively analyzed the modifications of arterial blood pressure according to response rate and PFS. Methods: Pts with histologically proven, mCRC receiving Bev in combination with Cht as first-line treatment were eligible. Arterial blood pressure was measured before each Bev administration and daily between subsequent cycles. Pts were re-staged every 8 weeks, according to RECIST criteria. Results: 53 pts were considered for the present analysis: 33 M and 20 F; median age was 59 years (range 34-78). Forty pts (75.5%) were affected by metastasis from colon cancer, 13 pts (24.5%) from rectal cancer. Twenty-eight pts had liver metastasis, 7 pts lung metastasis, 7 pts had metastasis at liver and lung. The remaining 11 pts had metastasis at peritoneum, nodes, bone or brain. Fifty pts had undergone surgery on primary tumor (38 colon; 12 rectal), and 18 pts had been treated with adjuvant ChT. First-line ChT regimens were: FOLFIRI (47 pts), XELOX (4 pts), XELIRI (2 pts). Thirteen pts were affected by pharmacologically controlled aHT. Nine pts (17%) developed G2-G3 aHT during the administration of ChT + Bev. After starting adequate anti-hypertensive therapy, they continued Bev until disease progression. All pts were evaluable for response: 15 (28.3%) had complete (3) or partial (12) response. Among pts with induced-aHT, 77.8% achieved a complete or partial response, as compared with 34.1% of pts who did not have aHT (p = 0.01). Median PFS in the whole population was 9.9 months (range 7-12.7). A statistically significant improvement in median PFS was recorded for pts with induced-aHT (18.7 vs 8.5 months; p = 0.02). Conclusions: Our data suggest that Bev-related aHT may represent a predictive factor of response and prolonged PFS in pts with mCRC receiving first-line Bev. No significant financial relationships to disclose.
Application of newer adjuvant treatments for node positive (N+) breast cancer (BC) patients (pts) in Italian centers. Results of the NORA (National Oncological Research Observatory on Adjuvant Therapy in breast cancer) Study
Authors: P. Pronzato, M. E. Cazzaniga, G. Mustacchi, F. Di Costanzo, A. de Matteis, L. Porcu, M. Danova, B. Salvadori, M. C. Chetrì, P. Rizzo
Journal: Journal of Clinical Oncology (2005)

878 Background: Taxanes and Aromatase Inhibitors (AI) have been demonstrated to improve the prognosis of early BC pts. Medical Community may be influenced by the relevance given to the solidity of results regarding established treatments or to the early reports of the new tratments and by the evaluation of baseline profile risk or of predictive factors. Methods: We are investigating adjuvant therapies in pts with BC, in the context of a national survey carried out in 77 Italian Centers during 2000–2003.We collected validated data about 2136 pts and analysed results on choices of adjuvant treatment. This report regards the choices of chemotherapy (CT) and Hormonotherapy (HT) in N+ pts with respect to prognostic and predictive factors. Results: We analyzed data concerning 941 N+ pts. The 713 ER+ and/or PgR+ pts were treated with HT alone in 16.8%, with CT and concomitant HT in 7.8% and with CT followed by HT in 75.3% of cases. Among 568 pts with 1–3 N+ TAM was applied in 66.7%, AI in 7.5%, Cyclophosphamide/Methotrexate/Fluorouracil (CMF) in 46.1%, a 2-drug anthracycline containing regimen (AC/EC) in 9.8%, a 3-drug anthracycline containing regimen (FAC/FEC) in 38.2% and a taxane including regimen (Tax) in 0.14% of cases. Among 232 pts 4–10N+ Tam was applied in 60.3%, AI in 9.9%, CMF in 14.2%, AC/EC in 7.7%, FAC/FEC in 53.8%, Tax in 9.0% of cases. Among 141 pts with >10N+ Tam was applied in 56%, AI in 11.3%, CMF in 13.4%, AC-EC in 11.3% FAC-FEC in 47.5% and Tax in 11.3% of cases. Among 360 HER/2 + pts Tam was applied in 67.5%, AI in 8.0%, CMF in 28.8%, AC/EC in 8.6%, FAC/FEC in 29.4%, Tax in 2.5% of cases. Among 296 ER+PgR- pts 81.4% received Tam and 9.7% an AI. The ratio between pts on Tam and pts on AI was 1:013 in the whole population,1:0.11 in HER/2+ pts, 1:0.12 in ER+PgR- pts. Conclusions: In the period 2000–2003 Tam remained the most largely employed HT both alone or in combination with CT. An anthracycline including regimen has been more frequently applied than CMF and FAC/FEC has been favourite over AC/EC mostly in pts at higher risk; Tax has been employed in a minority of cases. ER+PgR- and HER/2 do not seem to have influenced the choices. No significant financial relationships to disclose.