tbuckley/cabot-search huggingface dataset:
Pemetrexed alone or in combination with cisplatin in previously treated patients with malignant pleural mesothelioma (MPM): Outcomes of an expanded access program (EAP)
Authors: M. Orlando, A. Wozniak, P. Janne, C. P. Belani, M. L. Keohan, H. Ross, J. Polikoff, D. Mintzer, L. Bloss, C. Obasaju
Journal: Journal of Clinical Oncology (2004)

7195 Background: The improved efficacy of pemetrexed (ALIMTA, Eli Lilly and Co) in combination with cisplatin versus cisplatin alone, in a phase 3 trial of patients with MPM, has led to a demand for patient access to pemetrexed prior to regulatory approval. An Eli Lilly and Co EAP was opened to allow access to all eligible patients with malignant mesothelioma. This non-randomized study was designed to gather additional efficacy and safety data on pemetrexed alone and in combination with cisplatin. The experience of those previously treated patients with MPM is reported here. Methods: Previously treated patients with malignant mesothelioma were enrolled in this study. Treatment consisted of pemetrexed 500mg/m2 alone or in combination with cisplatin 75mg/m2. Treatment was administered once every 21 days for a maximum of 6 cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilence database. Results: To date, 127 previously treated patients (97M/30F) with pleural mesothelioma have been enrolled. Median age was 65.0 (range = 25.0 to 83.0). An analysis of best tumor response included 31 evaluable patients, which included 4 PRs (12.9%), 6 SDs (19.3%), and 21 PDs (67.7%). The SAE database includes all patients from the EAP with either pleural or peritoneal mesothelioma. SAEs, irrespective of causality, were reported by number of events: nausea (44), vomiting (41), diarrhea (21), renal insufficiency (21), asthenia (13), atrial fibrillation (13), cellulitis (9), constipation (8), dysphagia (4), rash (2), neuropathy (2), stomatitis (2), anemia (12), thrombocytopenia (7), neutropenia (7), and neutropenic fever (4). Conclusions: Pemetrexed with or without cisplatin in previously treated patients with pleural mesothelioma has a favorable safety profile. The clinical benefit rate of 32.2% indicates activity in this poor prognostic patient population. This trial will conclude in early 2004, and all response and safety data will be forthcoming. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.
Determinants of failure of venous access devices in outpatient oncology
Authors: R. Sanjay, K. Bielagus, T. Mohamed, M. Krentzin, R. Weinstein
Journal: Journal of Clinical Oncology (2006)

8613 Background: Little guidance is available regarding the optimum placement and use of implantable venous access devices (VAD) in cancer treatment. We present herein 10 years of experience with VAD in a university hospital oncology clinic. Methods: Post hoc analysis of prospectively collected records of 346 cancer patients in whom 362 VAD (Port-a-Caths) were placed between January 1995 to December 2005. Primary end points included need for instillation of tissue plasminogen activator (TPA) to restore patency, need for an x-ray dye study to determine catheter salvageability, and premature removal because of VAD failure. We used Chi-square analysis to compare VAD placement by the Radiology service under fluoroscopy vs. placement by Surgery in the operating room (OR), placement in the right vs. left chest and internal jugular (IJ) vs. subclavian (SC) vein placement. Results: OR-placed VAD, more often than Radiology-placed VAD required TPA for patency (18.6% vs 8.07%, p&lt;0.01), a dye study (11.7% vs 2.69%, p=0.001) or premature removal (14.7% vs 5.38%, p&lt;0.01). Right- and left-sided VAD were equally likely to receive TPA (9.2% vs 16.1%, p=0.11) but left-sided VAD required more dye studies (3.3% vs 10.7%, p=0.013) and were prematurely removed more often (5.5% vs 15%, p=0.007). 29 (8%) of VAD were prematurely removed because of infection (n=11), thrombosis(n=6), pain (n=2), mechanical malfunction (n=6) and others (n=4). Gender, age (&lt; vs. &gt; 60 years), site of placement (IJ vs. SC) or body mass index (&lt; vs. &gt; 25) had no bearing on the primary endpoints. Intrathoracic cancer was associated with more TPA treatment of the VAD (16.8% vs. 8.4%, p&lt;0.023) but not with dye studies (7.9% vs. 4%, p=0.191) or removal (6.1% vs. 8.8%, p=0.517). Conclusions: AVAD will usually last until completion of cancer therapy. Occlusion or premature removal is less likely in a VAD placed on the right side under fluoroscopic guidance by an experienced radiologist. Thoracic disease, site of placement, obesity, age or gender do not determine adverse outcomes for VAD. No significant financial relationships to disclose.
Hypofractionated three-dimensional conformal radiotherapy alone in locally advanced, non-small cell lung cancer medically unfit to multimodality treatment.
Authors: S. Song, Y. Lee, Y. Kim, S. Yoon, S. Lee, S. Ahn, J. Kim, D. Lee, J. Lee, E. Choi
Journal: Journal of Clinical Oncology (2010)

e17527 Background: To retrospectively review the outcome of definitive hypofractionated 3-dimensional conformal radiotherapy (3D-CRT) alone in locally advanced non-small cell lung cancer (NSCLC) medically unfit to multimodality treatment. Methods: 102 patients with clinical stage IIB-III NSCLC received 3D-CRT alone from Jan 2002 to Jul 2007. Among them, 37 patients were analyzed. The other 65 patients were excluded due to the history of another cancer, incomplete treatment or loss of follow-up without severe RT-associated complication. Reasons of radiotherapy (RT) alone were the poor pulmonary function, old age with poor performance or others. Median age was 72 years and most patients were male. Two-thirds patients had squamous cell carcinoma (SCC) and sixty-percent of patients had stage IIB disease. Radiotherapy dose was 66 Gy in 30 fractions. Elective nodal irradiation was not done. Tumor response was evaluated 1 month after radiotherapy using RECIST criteria. Results: Tumor response was judged to major response in 20 (54%), stable disease in 16 (43%), and disease progression in 1 (3%) patients. During the follow-up period, 20 patients (54%) suffered from disease recurrence and the first failure site was locoregional progression in 10, distant metastasis in 5 and both in 5 patients. Median follow-up period was 14 months. Median survival time was 15 months and 2 year overall survival was 37%. Locoregional progression occurred in 15 patients and 2 year locoregional progression-free survival was 44%. T stage and tumor response were significant factors for survival. Radiotherapy-associated toxicities were not severe. No G3 or above radiation esophagitis was noted, but two patients suffered from G3 and G4 radiation pneumonitis. No treatment-related death was revealed. Conclusions: Major pattern of failure after hypofractionated 3D-CRT alone in selected patients medically unfit to multimodality treatment was the locoregional progression, although they had locally advanced NSCLC. The prospective investigation for the escalation of radiotherapy dose is needed to improve the locoregional tumor control after radiotherapy alone in NSCLC. No significant financial relationships to disclose.
Fluorouracil, leucovorin and oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP) as a first line therapy for patients with advanced gastric cancer; first interim analysis of a randomised multicenter phase II study
Authors: S.-E. Al-Batran, J. Stöhlmacher, S. Probst, S. Hollerbach, G. Wilhelm, H. G. Derigs, G. Seipelt, G. Kojouharoff, M. Graubner, A. Hinke, E. Jäger
Journal: Journal of Clinical Oncology (2005)

4015 Background: To evaluate the potential role of oxaliplatin in the treatment of patients (pts) with advanced gastric cancer. Methods: Eligible patients had ECOG performance status (PS) 0–2, adequate liver, renal, and haematological function. Pts were randomised to receive FLO: F 2600mg/m2 24h infusion, L 200mg/m2, and oxaliplatin 85mg/m2 every two weeks or FLP: F 2000mg/m2 24h infusion, L 200mg/m2, weekly, and cisplatin 50mg/m2 every two weeks. The primary end point was the 6-month progression free survival rate. A protocol planned interim analysis to evaluate response and safety was performed when 80 patients had been randomized and completed at least one treatment cycle. Results: 105 pts have been randomised. Data on 80 pts were available for toxicity and response (see table). Conclusions: The overall toxicity was low in both arms. The activity of FLO appears promising. Since grade 3/4 non-haematological toxicity affected less than 10% of patients in both arms, no dose adjustments were performed and accrual will continue to the target of 180 patients. No significant financial relationships to disclose.
Incidence and significant predicting factors for chemotherapy-induced severe thrombocytopenia in lymphoma patients
Authors: X. Zhou, A. Huen, S. Teegala, Y. Ji, L. E. Fayad, F. B. Hagemeister, S. Vadhan-Raj
Journal: Journal of Clinical Oncology (2008)

20519 Background: Severe thrombocytopenia (TCP) is a complication of chemotherapy (CT), resulting in frequent transfusions and treatment delays. The incidence and risk factors for TCP in lymphoma patients (pts) with current CT regimens are not well defined. Methods: Medical records of 1046 newly referred lymphoma pts to MD Anderson Cancer Center in 2003 were retrospectively reviewed over two years follow-up period. The incidence of severe TCP was determined, and logistic regression models were employed to identify the significant baseline clinical and laboratory features correlated with severe TCP. Results: 404 pts, who received ≥ 1 cycle of treatment and had adequate laboratory records, were included in the analysis (total CT cycles 2061). Grade (GR) 4 TCP (PLT nadir < 25×103/μL) was observed in 42% (170/404) of pts, in the median cycle 2 (range 1-11) and median PLT nadir of 12×103/μL (1- 24×103/μL). Bleeding occurred in 48% (81/170) of pts with GR 4 TCP compared to 8% (19/234) of pts with higher PLT counts (p=0.0001), although most bleedings (95%) were minor. Seventy-nine percent (134/170) of pts with GR 4 TCP received PLT transfusions, compared to only 2% (4/234) of pts with higher PLTs (p<0.0001). 137 out of 170 (81%) GR 4 TCP pts and 245 out of 398 (62%) GR 4 TCP episodes occurred in the 1st regimen. Therefore the logistic regression models analyzed the data set of 1st regimen. In the multivariate model, following variables were most important predictive factors for GR 4 TCP. Conclusions: The incidence of severe TCP in lymphoma pts is high. Predictive risk factors can be very useful to develop prophylactic strategy with PLT growth factors in high risk pts to prevent TCP related complications. Variable Odds Ratio (95% CI) P value Myelosuppressive Risk of Regimen ( high vs low) 38.60 (18.70–79.66) <0.0001 Extra Nodal Involvement (yes vs no) 2.57 (1.29–5.09) 0.007 Type of Previous Therapy* (CT+RT vs no Rx) 3.53 (1.33–9.33) 0.011 PLT Count 0.995 (0.993–0.998) 0.001 Serum Beta2MicroG 1.153 (1.03–1.29) 0.014 * RT: radiotherapy; no statistical significance between RT or CT±surgery vs no Rx. No significant financial relationships to disclose.
Impairment of cognitive function in patients submitted to adjuvant chemotherapy for early breast cancer: A follow up study
Authors: M. Guida, M. R. Barulli, C. Stangalino, L. Mariani, A. Caraceni, V. Lepore, P. Livrea, M. F. De Caro, G. Gallus, V. Lorusso
Journal: Journal of Clinical Oncology (2004)

8027 Background: There is increasing evidence that the degree and duration of cancer treatment may contribute to cognitive impairment. However, the precise role of standard adjuvant chemotherapy (ACT) in early breast cancer patients in the development of these impairments needs to be further investigated. Methods: The study design is longitudinal providing follow-up 12 months later. The treated group consisted of 53 breast cancer survivors (age, 60.3±4,3 yr) who were treated with ACT (5 yr since the end of cancer treatment). Patients (pts) were treated with CMF (n=24), ADM (n=4), CMF+ADM (n=25) plus (n=37) or minus (n=16) tamoxifene. The control group consisted of 71 breast cancer survivors (age, 63.4±4,1 yr) not treated with ACT (5 yr post-surgery). All pts were assessed using the following neuropsychological tests: two cognitive deterioration-screening tests (MODA and MMSE); 12 analytic tests (Prose memory test, Word list learning test, Digit cancellation test, Trail making test, Verbal span, Raven Coloured progressive matrices, Elithorn's perceptual maze test, Token test, Verbal phonemic fluency, Verbal semantic fluency, Street's completion test, Figure copying test). Results: Comparisons between the two groups did not reveal statistically significant differences on MMSE (treated group 29,6±0,9; control group 29.7±0.8) and MODA (treated group 94,4±3.3; control group 95.2±2.6) scores. Analysis of performance, in the 12 neuropsychological tests, showed statistically significant differences between the groups on Prose Memory Test (Wilcoxon Test, P=0,03) and Verbal Fluency Test (Wilcoxon Test, P=0,01).The treated group performances on the Prose Memory and on the Verbal Fluency scores were significantly worse than those of the control group. Conclusions: The preliminary results of this study show the presence of statistically significant difference on episodic memory and phonemic lexical access abilities between the groups. We propose that all pts over 55 yrs undergoing ACT should be submitted to a basal evaluation of cognitive function. This study was supported by grant from Healthy Ministry, PRF Conv. N.ICS 160/RA00.72 No significant financial relationships to disclose.
Evaluating safety and efficacy of AMG 531 for the treatment of thrombocytopenic patients with myelodysplastic syndrome (MDS): Preliminary results of a phase 1/2 study
Authors: H. M. Kantarjian, F. J. Giles, P. Fenaux, P. S. Becker, A. M. Boruchov, D. T. Bowen, E. Hellström-Lindberg, R. A. Larson, R. M. Lyons, P. Muus
Journal: Journal of Clinical Oncology (2007)

7032 Background: The prevalence of thrombocytopenia in MDS ranges from 40% to 65%, hemorrhagic complications range from 3% to 53%, and hemorrhagic deaths range from 14% to 24% (Kantarjian 2006). Platelet transfusion can lead to reactions, infection, and alloimmunization. AMG 531 is a thrombopoiesis-stimulating peptibody that increases platelet production. This phase 1/2 study evaluated the safety and efficacy of AMG 531 in thrombocytopenic MDS patients. Methods: A minimum of 5 subjects with low risk MDS (IPSS low or intermediate-1) and a platelet count of = 50×10 9 /L were enrolled to receive 3 QW SC injections of AMG 531 in each of 4 sequential dose cohorts. After evaluation at week 4, subjects could continue AMG 531 in an optional treatment extension at their assigned dose or escalated to a responding dose. Erythroid growth factors were allowed, but no other active treatment. Results: 28 subjects (9 transfusion-dependent) have been enrolled to date. All subjects were evaluable for response and entered the extension; 17 continue treatment. Dose-limiting toxicity (DLT) was defined as a drug-related grade 3 or 4 adverse event (AE) or a platelet count ≥ 600×10 9 /L. Two DLTs occurred, both due to elevated platelet counts. No treatment-related severe AEs occurred. There was 1 treatment-unrelated death. Overall, 17 subjects (61%) achieved a platelet response. Median baseline platelet count for responders was 25×10 9 /L with a median peak platelet count of 130×10 9 /L during the 4 week treatment period. Of the 18 subjects to date completing at least 12 weeks of treatment, 11 (48%) achieved a durable response of at least 8 consecutive weeks (revised IWG criteria, Cheson 2006). A total of 90 clinically significant thrombocytopenic events (39 bleeding, 51 transfusions) were observed over both treatment phases. There were 16 such events (12 bleeding, 4 transfusions) in 6 subjects with a durable response, 6 events (6 minor bleeds, 0 transfusions) during the durable response period. There were 74 events (27 bleeding, 47 transfusions) in 11 subjects without a durable response. Conclusions: These preliminary data suggest that bleeding and transfusion events can be reduced in thrombocytopenic low risk MDS patients who respond to AMG 531. [Table: see text]
Phase II trial of high-dose bolus IL-2 in patients with metastatic melanoma (mm) who have previously failed biochemotherapy (BCT)
Authors: S. S. Agarwala, W. Gooding, G. D'Angelo, J. M. Kirkwood, L. L. Stover, J. Baar, J. Shipe-Spotloe
Journal: Journal of Clinical Oncology (2004)

7512 Background: BCT comprising combination chemotherapy, infusional IL-2 and IFN-alfa has produced high response rates (40–50%) in phase II studies, but recent randomized trials have failed to show a superiority for BCT over CT alone. High-dose bolus (HDB) IL-2 can produce long-term remissions in 6–10% of previously untreated patients with MM and utilizes considerably higher doses of IL-2, raising the question of whether HDB IL-2 may have activity in patients who have progressed following BCT. Methods: A phase II trial of HDB IL-2 for patients who had progressed following BCT was conducted at the University of Pittsburgh. Eligible patients had measurable disease, PS 0–1 and had progressed on or after BCT (cisplatin, vinblastine, dacarbazine, IL-2, 9 MU/m2/day × 4 days, and IFN-alfa 2b). HDB IL-2 was administered at 600,000 U/kg per dose, for a maximum of 14 doses per cycle with a one-week rest period between cycles. Stable or responding patients were offered an additional course of therapy after 6–8 weeks. Treatment was conducted on an in-patient oncology unit with trained personnel. Results: To date, 26 patients (12 male, 14 female) age 26–70 (median 44) years have been treated. All but 3 patients received at least two cycles (one course) of HDB IL-2; 10 patients recieved a second course of therapy. The median number of doses administered was 9 (range 6–14) during cycle 1 and 7 (range 2–12) during cycle 2. Disease stage was AJCC Mla (5) Mlb (5) and Mlc (16). Grade 3 toxicities included hyperbilirubinemia (10), thrombocytopenia (6), tachycardia (5), hypotension (4), oliguria (3), diarrhea (1), infection (2) and neurologic (2). Grade 4 toxicities included thrombocytopenia (1) and hyperbilirubinemia (1). Overall response rate was 19% (4 complete, 1asting 4, 4, 5 and 12+ months, 1 partial, lasting 3 months). Seven patients (27%) had SD lasting 1–3 months, but all eventually progressed. All 4 complete responders were AJCC Stage Mla. Median survival is 26.4 weeks for the entire group (95% CI 11.4–57.6 weeks). Conclusions: HDB IL-2 is active in patients with MM who progress on BCT, an observation that has implications for dose intensity with this agent. No significant financial relationships to disclose.
A low-dose combination therapy of IL-2 and IFNα for metastatic renal cell cancer
Authors: H. Akaza
Journal: Journal of Clinical Oncology (2004)

4670 Background: In Japan, the officially recommended dose of interleukin-2 (IL-2) is low as less than one tenth of that in U.S.A. This study was done to confirm the usefulness of low-dose IL-2 plus interferon-α (IFN-α) against metastatic renal cell carcinoma. Methods: In step 1, the dose of IL-2 (teceleukin) was fixed at 0.7×106 JRU (IU)/body on 5 days/week, i.v., and the dose of IFN-α (Human Lymphoblastoid interferon) was increased from 3×106 IU/body on 3 days/week (level I) to 6×106 IU on 3 days/week (level II) and to 6×106 IU on 5 days/week (level III). All patients entered into the study were renal cell carcinoma with metastasis, and had nephrectomy. Results: In step 1, 10 patients were registered, and 9 (3 at each level) could be evaluated. Since grade 3 and grade 4 neutropenia was observed in 1 patient each at level III, level II was determined as the recommended regimen. The response rate in step 1 was 44.4% (4/9), and it was 66.7% (4/6) in the patients who had only lung metastases. In step 2, 46 patients were registered, and the response rate in the 37 patient who were classified as PPS (per protocol set) was 21.6% (8/37), and that in those with only lung metastases was 33.3% (8/24). The side effects observed were primarily ful-like symptoms due to cytokines, and gastrointestinal symptoms, leukocyte abnormalities, and abnormalities of the liver function were noted, but they were milder than those reported at a large dose of IL-2. Conclusions: In the 46 patients evaluated in step 1 and step 2 combined, the response rate was 26.1% (12/46), and it was particularly high at 40.0% (12/30) among those with only lung metastases, so that the combination therapy of low-dose IL-2 and IFN-α was suggested to be an effective and safe regimen for this patients group. No significant financial relationships to disclose.
Characteristics and treatment patterns in patients newly diagnosed with chronic lymphocytic leukemia (CLL).
Authors: G. P. Hess, C. Chen, S. Satram-Hoang, C. M. Reyes
Journal: Journal of Clinical Oncology (2010)

e16561 Background: CLL is the most common form of adult leukemia. This study aimed to describe clinical and demographic characteristics, and treatment patterns in newly diagnosed CLL patients. Methods: Qualifying patients were diagnosed with CLL between 1/1/2004 and 12/31/2007, were ≥18 years old and had two years of follow-up in the SDI health care claims databases. Patients were classified into the following treatment groups: no treatment, chemotherapy only (chemo), rituximab only (R), and rituximab plus chemotherapy (R+chemo). Patient characteristics and treatment patterns in frontline and relapsed CLL were analyzed. Results: Of 9,136 patients who met the study criteria, the majority (54%) were > 70 (mean age =69 years); 52% male; 85% Caucasian; 93.5% had a non-cancer Charlson Comorbidity Index of <1; 51.3 % were Medicare insured; and a median income of $62,500. Among those treated (n=612, 6.7%), 66.7% received chemo, 13.4% received R, and 19.0% received R+chemo as their initial treatment. Patients over 65 years (69.6%) were less likely to receive oncologic treatment in the first year. Among those treated, the R group had the highest proportion of patients over 70 years old (49.2%), compared to 26.6% in R+chemo, and 40.4% in the chemo only group. For those treated (n=612), the median time from diagnosis to frontline treatment was 153 days and 102 days for chemo only and R, respectively (p=0.235). Compared to frontline CLL, those who relapsed and received 2nd line treatment (n=120; 19.6%) received relatively more R and R+chemo (52.5%) than chemo alone (45.8%). Conclusions: In a large 2-year retrospective cohort of patients diagnosed with CLL, approximately 6.7% received systemic therapy. Among those patients treated, chemo was the most common frontline regimen, and R and R+chemo were the most common regimens for relapsed CLL. Similar treatment patterns were observed in patients older than 70 years old. Treatment patterns Patients % No treatment 8,524 Frontline CLL 612 Chemotherapy 409 66.8% Rituximab/alemtuzumab 82/5 14.2% Rituximab + chemotherapy 116 19.0% Relapsed CLL 120 Chemotherapy 55 45.8% Rituximab/alemtuzumab 37/2 32.5% Rituximab + chemotherapy 26 21.7% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech