tbuckley/cabot-search huggingface dataset:
Phase I study of ZD1839 plus temozolomide in patients with malignant glioma. A study of the North American Brain Tumor Consortium
Authors: M. Prados, W. Yung, P. Wen, L. Junck, K. Fink, T. Cloughesy, I. Robins, S. Chang, J. Kuhn
Journal: Journal of Clinical Oncology (2004)

1504 Background: To define the MTD of ZD1839 in combination with Temodar in patients with malignant glioma, without (Group A) or with (Group B) enzyme-inducing antiepileptic drugs (EIAEDs). Methods: Eligible pts were > 17 years of age, had KPS ≥60 with stable or progressive malignant glioma, with acceptable laboratory baseline tests. Radiation was completed at least 3-weeks prior to registration. No more than 3 prior chemotherapy regimens allowed. Treatment: Patients started on a continuous dose of ZD1839 (day 1) beginning at 500 mg/day. Temodar started (day 8) at an oral dose of 150 mg/m2/day for 5 days after the ZD1839 and was repeated every 28 days. Temodar could be escalated to 200 mg/m2/day after cycle 1. DLT was defined as any grade 3 or greater non-hematological or any grade 4 hematological toxicity using CTC v 2.0 during the first 35 days of therapy. 3 patients per cohort (Group A or Group B) were enrolled. The dose of ZD 1839 was escalated by 250 mg increments assuming no DLT in each 3-patient group. If 1 DLT was seen in 3 patients, 3 additional patients were enrolled at that dose. The MTD was the dose level at which 0/3 or 1/6 patient experienced DLT with the next higher dose having at least 2/3 or 2/6 patients with DLT. Patients could continue treatment indefinitely until tumor progression or unacceptable toxicity. Results: 28 pts enrolled (12 in Group A, 16 in Group B); 20 had GBM, rest with grade-3 tumors; all had prior XRT, 9 were chemo naïve. For Group A pts, the MDT of ZD 1839 was 250 mg/day, one dose level lower than the starting dose. DLT's at 500 mg were grade 3 diarrhea and ALT elevations. There were no DLTs at 250 mg/day. For Group B pts, the MTD of ZD 1839 was 1000 mg/day. DLT's at 1250 mg included grade 3 diarrhea, vomiting, hyponatremia and weakness, and grade 4 hypokalemia. Skin rash was always ≤ Grade 2. Conclusion: The recommended phase-2 dose of ZD1839 plus Temodar in patients on EIAEDs is 1000 mg/day, and 250 mg/day for patients not on EIAEDs. No significant financial relationships to disclose.
Phase I study of nab-paclitaxel and gemcitabine combination in patients with advanced pancreatic cancer
Authors: R. L. Drengler, L. S. Smith, T. E. Wood, M. J. Borad, R. K. Ramanathan, D. A. Laheru, M. Hidalgo, D. D. Von Hoff
Journal: Journal of Clinical Oncology (2008)

15523 Background: Most patients (pts) with pancreatic cancer present with advanced disease with a survival range of about 6–7 months (mo). Currently gemcitabine (gem) or gemcitabine plus erlotinib is standard treatment for pts with advanced pancreatic disease. The benefits of combination therapy with gemcitibine have been modest. Nab-paclitaxel (nab-pac) is a novel formulation of paclitaxel approved for the treatment of breast cancer. It allows for the preferential delivery of active drug to the site of the tumor, as demonstrated in many preclinical tumor models. In this phase I study, the combination of nab-pac and gem in pts with pancreatic cancer is evaluated. Methods: Pts with no prior chemotherapy except as a radiation sensitizer received nab-pac + gem on days 1, 8, 15 every 28 days, with a dose of 100 mg/m2 and 1,000 mg/m2 respectively in this modified Phase I trial (cohort 1). Cohort 2 (nab-pac 125 mg/m2) is ongoing. Results: 20 pts have been enrolled on cohort 1. All are evaluable for toxicity, 16 for response. Pts had a median (med) age 57 (30–86); gender: M:F 55%/45%. (Med cycles administered 5 (range 1–8). Response by radiographic review and RECIST criteria was assessed in 16 pts: 9 PR, 6 SD, 1 PD. The med cycles to response was 2 (1 -5). The MTD has not been reached and a DLT has not been reached. The most frequent Grade 3/4 adverse event (AE) was neutropenia (n=3, 2, respectively). Other grade 3 AEs include febrile neutropenia (1), fatigue (1) and hyperglycemia (1). In addition, 2 cases of grade 2 anemia and 2 cases of thrombocytopenia were observed. To date, no grade 3/4 sensory neuropathy was observed. Additional follow up data on cohort 1 and results from cohort 2 will be presented. Conclusions: These preliminary results suggest that nab-pac in combination with gem is very active in pts with advanced pancreatic cancer. Toxicities were tolerable and manageable. This combination will be further evaluated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Concordia, Genentech™ BioOncology Abraxis, Bunso, Cell Genesys, Cenis, Concordia, Genentech™ BioOncology, Genvec
No advantage of chemoradiotherapy over chemotherapy alone in elderly patients with localized low risk aggressive lymphoma: results of the LNH93-4 GELA study.
Authors: Georges Fillet, Christophe Bonnet, N. Mounier, N. Ganem, T. Molina, C Thieblemont, C. Fermé, B. Quesnel, C. Martin, C. Gisselbrecht, H. Tilly, Reyes
Journal: Annals of Oncology (2005)
Randomized, active-controlled phase IIb study with trabedersen (AP 12009) in recurrent or refractory high-grade glioma patients: Basis for phase III endpoints
Authors: U. Bogdahn, T. Schneider, V. Oliushine, V. Parfenov, A. K. Mahapatra, A. Balasubramaniam, N. Venkataramana, G. Stockhammer, H. Heinrichs, K. Schlingensiepen
Journal: Journal of Clinical Oncology (2009)

2037 Background: High-grade gliomas (HGG) strongly overexpress TGF-beta 2. Trabedersen (AP 12009), a TGF-beta 2-specific inhibitor, was successfully tested in 3 Phase I/II studies in recurrent or refractory HGG. Methods: The Phase IIb study AP 12009-G004 was an open-label, randomized, active-controlled dose-finding study. Main objectives: to compare response rate, survival, and safety of 2 doses of trabedersen (10 μM or 80 μM) vs. standard chemotherapy (TMZ or PCV). 145 patients with recurrent or refractory HGG (AA WHO grade III or GBM WHO grade IV) were randomized and 134 patients (AA = 39; GBM = 95) received study medication. Trabedersen was given intratumorally by convection-enhanced delivery. Results: AA and GBM patients in both trabedersen groups had long-lasting tumor responses (currently up to 4 years). AA: (10 μM trabedersen vs. control): significantly better overall response rate was noted at 14 months (CR+PR; p=0.034*) and lower tumor progression rates at 6, 12 and 14 months; difference at 14 months was statistically significant (p=0.003*). 2-year survival rate was 2-fold higher (p=0.088**). Tumor progression rate at 14 months and 2-year survival rate correlated with a median overall survival benefit of 17.4 months. GBM: 10 μM trabedersen was as efficacious as standard chemotherapy in all patients. It was clearly superior regarding 2-year survival in the pre-specified subgroup of patients younger than 55 years and the subgroup with a KPS &gt; 80. The superior long-term survival of trabedersen-treated AA and GBM patients was the basis for extending the follow-up period of this Phase IIb study. Conclusions: Based on Phase IIb results, the pivotal Phase III study SAPPHIRE in recurrent or refractory AA patients has started. Primary efficacy endpoint is 2-year survival rate; secondary endpoints are progression rate at 14 months, time to death, quality of life, safety and tolerability. A separate study in GBM is being planned. [Table: see text] [Table: see text]
Patterns of hospitalization and toxicity among patients undergoing cancer chemotherapy in community-based oncology practice in Brazil
Authors: P. E. Pizao, L. M. Katayama, A. J. Sagarra
Journal: Journal of Clinical Oncology (2007)

19678 Background: In Brazil, most cancer patients receive treatment outside the controlled clinical trial setting and at community- based clinics. In this scenario, data on treatment-related toxicity and its complications are seldom reported. Chemotherapy is frequently referred to as an excessively toxic treatment modality and this perception may have a negative impact on treatment decision-making. Methods: This is a single institution, prospective study. Eligible population consisted of all patients with solid tumors undergoing chemotherapy, between January/2005 and November/2006, at this community-based private oncology clinic with a multidisciplinary staff (physicians, nurses, pharmacists, nutrition and psycology experts). Treatment-related hospitalization (TRH) was defined as any hospitalization starting within 4 weeks after a chemotherapy session. Data concerning tumor-related symptoms and chemotherapy-induced toxicity were prospectively collected by a single physician. Results: A total of 59 patients were hospitalized during the study period. Median hospitalized patients′ age was 61 years and 58% were female. Most frequent tumor types were breast (36%), colorectal (14%), pancreatic (14%) and ovarian (9%) cancers. 34 (57%) of the 59 hospitalizations were classified as TRH. Febrile neutropenia (27%) and gastrointestinal complications (26%) were the main reasons for TRH. The median length of TRH was 4 days. 6/34 (17%) patients died during TRH: 5 died as a result of complications caused by disease progression (not chemotoxicity); 1 patient died as a consequence of chemotherapy-induced neutropenia and sepsis. TRH′s were associated to only 2% (34) of the 2203 chemotherapy sessions performed. Conclusions: Current evidence-based, consensus-guideline-oriented, cancer chemotherapy, administered by a multidisciplinary team of specialists, was associated to a low rate of treatment-related hospitalizations. Generally, chemotherapy-induced toxicity was reversible and manageable in the outpatient setting. The permanent monitoring and reporting of treatment-related toxicities is feasible in community-based clinical practice as part of a quality-assurance program. No significant financial relationships to disclose.
Race and colon cancer: Unanswered questions.
Authors: R. Sehgal, C. C. Larck, Y. Dementieva, M. R. Tria Tirona, P. Edwards, W. M. McHayleh, B. C. Lembersky
Journal: Journal of Clinical Oncology (2010)

1525 Background: Impact of race on prognosis of colon cancer (CCa) is controversial and the potential reasons for that are not clearly understood. We analyzed data from Cancer Information Reference File (CIRF) database to study factors that might affect survival in African American (AA) and White (W) patients (pts) with CCa. Methods: Of 37,394 pts diagnosed with CCa from 1993-2008, complete data (age, sex, disease status, tumor characteristics, treatment and overall survival) were available for 35,310 pts (32,614 W and 2,696 AA). Results: Median age at diagnosis was 73 years (yrs) for W vs 66 yrs for AA pts (p < 0.0001). Total of 27% of W vs. 14% of AA pts (p < 0.0001) were ≥ 80 yrs of age at time of diagnosis while 7% of W vs. 12% of AA pts (p < 0.0001) were <50 yrs of age at time of diagnosis. Stage IV, high-grade tumor and right sided tumor were present in 18% vs. 14% (p < 0.0001), 21% vs. 15% (p < 0.0001), 52% vs. 51% of W and AA pts, respectively. Less than 12 lymph nodes were retrieved at surgery in 44% of W vs. 41% of AA pts (p - 0.009). Overall, 34% of W vs. 37% of AA pts received chemotherapy. Median overall survival for pts < 70 yrs of age was 109 months (mnths) vs. 91 mnths (p - 0.0008) and for pts ≥ 70 yrs was 48 mnths vs. 40 mnths (p - 0.0005) for W and AA pts, respectively. On multivariate cox regression analysis, race was an independent prognostic factor for survival, with AA having a 20% higher risk of death compared to W pts in both < 70 yrs (HR - 0.8, p < 0.0001) and ≥ 70 yrs old pts (HR - 0.8, p < 0.0001). Conclusions: AA pts present at a much younger age and advanced stage of CCa at the time of diagnosis. Despite lower grade, optimal surgery and similar rates of chemotherapy, all AA pts (younger and older) with CCa have a worse survival than W pts. This could be due to biological differences of tumors yet to be identified or other comorbidities in AA pts.Older pts in both groups have significantly poor survival as compared to younger pts. No significant financial relationships to disclose.
CHOP-R therapy overcomes the adverse prognostic influence of BCL-2 expression in diffuse large B-cell lymphoma (DLBCL)
Authors: K. S. Wilson, L. H. Sehn, B. Berry, M. Chhanabhai, J. M. Connors, C. A. Fitzgerald, K. K. Gill, R. Klasa, B. Skinnider, R. D. Gascoyne
Journal: Journal of Clinical Oncology (2004)

6526 Background: Following the demonstration of superior survival with CHOP-R for pts >60 years with advanced DLBCL (GELA, ASH 2000, abst # 950), the BC Cancer Agency adopted CHOP-R for advanced DLBCL in March 2001. CHOP-R therapy is thought to negate the adverse effect of BCL-2 protein expression on response rates and survival (Mounier et al, Blood 2003). We report our experience to determine whether BCL-2 status remains a significant prognostic factor in advanced DLBCL for pts who receive CHOP-R. Methods: Eligibility: age >16 yrs; de novo DLBCL; HIV neg.; no CNS involvement; available BCL-2 protein expression. All pts had central histopathology review. BCL-2 tumor positivity was defined as 50%+ of tumor cells with BCL-2 protein expression. Treatment plan: for stage IA or IIA with bulk <10 cm, suitable for IFRT (limited stage), CHOP-R x 3 cycles + IFRT; for all other patients (advanced stage), CHOP-R for 6 –8 cycles depending on rate of response. High dose therapy (HDCT) with stem cell transplant was offered to suitable relapse/PD pts. who demonstrated response to multi-agent chemotherapy. Results: Between March 2001 and November 2003, 89 pts, median age 63 y (range 20–84) received CHOP-R; limited stage 3%, advanced 97%; IPI distribution: 0–1 (34%), 2–3 (45%), 4–5 ( 21%), elevated LDH (49%), bulky disease >10cm (27%). BCL-2 positive 55 (62%). IPI score was similar in both BCL-2 positive and negative sub-groups. Median follow-up time for living pts. is 16 months. Neither BCL-2 protein status nor IPI group was significantly predictive of PFS or OS (see table). Conclusions: The introduction of CHOP-R in British Columbia appears to negate the adverse effect of BCL-2 protein expression on survival in DLBCL and may decrease the impact of higher IPI score. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Canada Roche Canada Roche Canada Roche Canada
Comparison of the sequential versus the alternate administration of cisplatin-etoposide and topotecan regimens as first line treatment in extensive stage small cell lung cancer (SCLC): A preliminary analysis of a multicenter randomized trial
Authors: V. Georgoulias, D. Mavroudis, M. Veslemes, P. Papakotoulas, K. Syrigos, A. Agelidou, G. Pavlakou, A. Rapti, A. Polyzos
Journal: Journal of Clinical Oncology (2004)

7045 Background: To compare the activity and tolerability of the sequential versus the alternate administration of cisplatin-etoposide and topotecan in patients with previously untreated extensive stage SCLC. Methods: 272 chemotherapy-naive SCLC patients have been enrolled into the study. Treatment consisted of either Arm-A(sequential): 4 cycles of cisplatin 75mg/m2 IV day-1 with etoposide 100mg/m2/d IV days 1–3 followed by 4 cycles of topotecan 1.5 mg/m2/d x5 days or Arm-B(alternate): cisplatin-etoposide at same doses on cycles 1,3,5,7 and topotecan on cycles 2,4,6,8. In both arms, cycles were repeated every 3 weeks without prophylactic growth factor support. Results: There is no statistically significant difference (p=NS) in any of the above comparisons between the two arms. A total of 1580 cycles of treatment have been administered (763 Arm-A; 817 Arm-B) with a median of 6.5 and 7 cycles/pt, respectively. Topotecan was administered in 87 pts of Arm-A and 128 pts of Arm-B. More cycles were delayed due to hematological toxicity in Arm-A 65 than Arm-B 44 (p=0.01). Dose reductions due to toxicity were similar in both arms. Toxicity (WHO criteria) per patient was (Arm-A/Arm-B): grade 3/4 neutropenia 54%/52% (p=ns), anemia 12%/14% (p=ns), thrombocytopenia 21%/17% (p=ns), febrile neutropenia 8%/7% (p=ns), asthenia 8%/2% (p=0.01). There were 5 toxic deaths in Arm-A versus 3 in Arm-B (p=0.5). Conclusions: From this preliminary analysis it seems that the two administration sequences result in comparable activity and tolerability in previously untreated patients with extensive stage SCLC. No significant financial relationships to disclose.
Mutation profile of JAK2 gene in patients with chronic myeloproliferative neoplasias
Authors: Wanlong Ma, Hagop Kantarjian, Xi Zhang, Chen-Hsiung Yeh, Zhong Zhang, Srdan Verstovsek, Maher Albitar
Journal: Clinical Cancer Research (2008)

B12   The V617F activating mutations in the Janus kinase 2 (JAK2) gene occur in a significant proportion of patients with Philadelphia-negative myeloproliferative neoplasias (MPNs). Additional mutations in exon 12 of JAK2 have been reported in rare cases of MPNs. Mutations other than these, however, have not been fully studied. It is believed that these mutations allow the activation loop of the kinase domain to move away from the pseudokinase domain, thus leading to constitutive activation of the JAK2-STAT pathway. We report that based on testing approximately 20,000 patients with clinical suspicion of MPNs, we detected new mutations in exons 13 and 14, in addition to those reported in exon 12, that in aggregate should be routinely tested for in patients with MPNs. Using a sensitive reverse transcription-polymerase chain reaction (RT-PCR) and direct sequencing approaches of plasma RNA, we detected mutations in approximately 20% of these patients. The exon 14 mutations include complete deletion of exon 14 (D596-N622 del), L624P, I641V, H606Q, and C618R. In exon 13, we detected R564L, R564Q, V567A, V567L, G571R, G571S, L579F, H587N and S591L. All these mutations are in the pseudokinase domain and are expected to inactivate the auto-inhibitory function of this domain on the kinase domain. This data suggests that testing for JAK2 mutations should not be restricted to the V617F and exon 12 mutations, but perhaps should include most of the pseudokinase domain. Furthermore, testing for mutations using plasma RNA is highly sensitive and should replace DNA-based testing because of the relative abundance of the RNA and the ease in detecting deletion of the entire exon.
Pertuzumab monotherapy following trastuzumab-based treatment: Activity and tolerability in patients with advanced HER2- positive breast cancer
Authors: J. Cortés, J. Baselga, T. Petrella, K. Gelmon, P. Fumoleau, S. Verma, X. Pivot, G. Ross, T. Szado, L. Gianni
Journal: Journal of Clinical Oncology (2009)

1022 Background: Pertuzumab binds to the dimerization epitope of the HER2 receptor, inhibits HER dimerization and signal transduction, and induces ADCC. In 2 cohorts of pts (n = 66) with HER2-positive metastatic breast cancer which had progressed during trastuzumab therapy after ≤3 lines of chemotherapy with or without trastuzumab, pertuzumab plus trastuzumab has been shown to be active (CR 7.6%, PR 16.7%, SD ≥6/12 25.8%) (Gelmon et al. ASCO 2008, Abs 1026). To assess the activity of pertuzumab monotherapy in this clinical setting, the protocol was amended to include a 3rd cohort of pts. Methods: Pt selection was not changed except that ≥1 month between the last dose of trastuzumab and study start was required. Pts received pertuzumab monotherapy. If the tumor failed to respond or responded and then progressed, trastuzumab could be added to pertuzumab. 27 pts were to be recruited to ensure that ≥24 were fully evaluable for objective response and stabilization of disease ≥6 months. Standard 21-day schedules of the antibodies were given. Results: 29 pts were recruited. Tolerability was good: the major adverse events were mild diarrhea and rash with no clinical cardiac events. To date, 2 responses have been reported, and several pts have ongoing stabilization of disease. 14 pts have received trastuzumab plus pertuzumab following inadequate response (or response then relapse) on pertuzumab monotherapy. Of these 14, 2, having progressed during trastuzumab, failed to respond to pertuzumab monotherapy but underwent confirmed response when trastuzumab was added to the pertuzumab –possibly the first report of such a phenomenon and providing good evidence of an enhanced effect when the antibodies are combined. Updated results will be presented. Conclusions: Pertuzumab monotherapy is active against HER2-positive breast cancer which has progressed during trastuzumab-based therapy. The combination of the two antibodies appears to be more active than either antibody alone. The combination is also active in patients that had failed both antibodies given separately. In clinical studies, the use of the two antibodies combined is justified. [Table: see text]
Reduced Expression of CD62L Is Associated with Increased ADAM17 Activity and Predicts Molecular Response to Nilotinib Therapy in Patients with Early Chronic Phase Chronic Myelogenous Leukemia (CML-CP)
Authors: Sieghart Sopper, Satu Mustjoki, Angelica Loskog, Bjorn T. Gjertsen, Ute Mark, Jens Haenig, Nidas Jurjonas, Gunther Gastl, Frank Giles, Andreas Hochhaus, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Journal: Blood (2014)
Early-stage male breast cancer: A 10-year experience
Authors: N. Gercovich, E. Gil Deza, M. Russo, C. Garcia Gerardi, C. Diaz, E. Morgenfeld, B. Rolnik, J. Emina, E. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2009)

e11630 Introduction: Male breast cancer is very rare, representing only between 0.7% and 1% of all breast cancers, and only half of them are early stage cases. Objective: The present study has been designed with the aim of studying retrospectively the clinical onset and evolution of male invasive breast cancer patients (stages I and II) treated at IOHM between 1997 and 2008. Methods: The records of 3,000 breast cancer cases followed between 1997 and 2008 were searched, looking for male stage I and II breast cancer patients. A database was designed following the recommendations of the Directors of Surgical Pathology of the USA. The information registered encompassed: adjuvant treatments, recurrence date and date of final consultation or death. Results: Twelve pts were identified. Mean age (range)= 66 yo (50–89 yo). Tumoral type= Invasive Ductal Carcinoma 12 pt. Tumoral subtype= NOS 9 pt (75%) Apocrine 2 pt (17%) Micropapillar 1 pt (8%). Nottingham´s grade= Grade 2: 8 pt, Grade 3: 3 pt, N/A=1 pt. Stage= I= 6 pt, II=6 pt. ER (Positve= 9 pt, Negative=1 pt, N/A= 2 pt). PR (Positve= 8 pt, Negative= 2 pt, N/A=2 pt). Her2neu (0+= 3 pt, 1+= 3 pt, 2+= 2 pt, N/A= 4 pt). Surgery= Mastectomy= 11 pt, Lumpectomy 1= pt. Radiotherapy=5 pt. Adjuvance= No=2 pt, Hormonotherapy (HT)= 3 pt, Chemotherapy (CHT) = 3 pt, CHT+HT= 4 pt. Recurrence= Yes= 2 pt, No= 10 pt. Survival: Dead= 1 pt, Alive =11 pt. Mean Time To Progression= Stage I =66 months, Stage II =42 months. Global survival: Stage I =66 months, Stage II =52 months. Conclusions: 1. Twelve stage I and II male breast cancer patients were identified out of 3000 (0.4%) breast cancer cases diagnosed and followed in the past 10 years at the IOHM. 2. Mastectomy was the surgical procedure in 11 of the 12 cases 3. Ten pt underwent adjuvant treatment. 4. With a mean follow up time of 60 months, all stage I patients are alive and there were no recurrences. Two of the 6 stage II pts progressed and one died. No significant financial relationships to disclose.