tbuckley/cabot-search huggingface dataset:
The influence of PET/Gallium (P/G) status and high-dose rituximab (HDR) in patients (pts) with aggressive, large, B-cell lymphoma (LBCL) receiving autologous stem cell transplants (ASCT)
Authors: A. M. Alousi, R. M. Saliba, G. Okoroji, C. Hosing, B. I. Samuels, R. E. Champlin, I. F. Khouri
Journal: Journal of Clinical Oncology (2006)

6518 Background: P/G status has been suggested to be an important predictor of outcome in pts with LBCL who receive an ASCT. Newer conditioning regimens which include HDR have been shown to improve results (Khouri, JCO, 2005). The influence of HDR on the outcome of pts based on P/G status has not been determined. Methods: A retrospective review of pts with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Results: A total of 188 pts were identified. Median age was 49 yrs with 108 (57%) male pts. 147 (78%) had de novo LBCL and 41 (22%) had an LBCL of follicular origin (LBCL-F). 83 (39%) pts received HDR with ASCT. At transplantation 95 pts (50%) were in PR, 71 pts (38%) in CRU and 22 pts (12%) in CR. 142 (76%) pts were P/G negative, 37 (20%) pts P/G positive and 9 (4%) pts unknown. The median follow-up was 44 months. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and P/G status. On multivariate analysis, P/G status and HDR were the only predictors for progression and PFS. Pts who were P/G negative and those that received HDR had a hazard ratio (HR) of 0.3 (p&lt;0.001) and 0.5 (p=0.02) for progression, respectively. The cumulative incidence (CI) of progression and progression free survival (PFS) at 54 months according to HDR and P/G status are shown in the table below. P/G Status and HDR were also found to be predictive for pts with LBCL- F on univariate analysis, however due to the small numbers in this subset of pts, multivariate analysis could not be performed. Conclusions: These results suggest that pre-transplant P/G positive status increases the risk of progression of LBCL after ASCT. The addition of HDR to the transplant regimen decreases this risk irrespective of P/G status. [Table: see text] No significant financial relationships to disclose.
Therapy-related myelodysplasia/ leukemia (t-MDS/AML) following treatment of children with Ewing sarcoma and primitive neuroectodermal tumor of bone (PNET)
Authors: S. Bhatia, M. Krailo, Z. Chen, L. Burden, P. Dickman, H. Grier, M. Link, P. Meyers, E. Perlman, L. L. Robison, J. Miser
Journal: Journal of Clinical Oncology (2005)

8514 Background: Limited information exists regarding risk of t-MDS/AML after Ewing’s sarcoma. Methods: We followed a cohort of 578 individuals less than 30 years of age, diagnosed with Ewing’s sarcoma, PNET or primitive sarcoma of bone between 1988 and 1994 (treated according to a therapeutic protocol: CCG-7881/POG-8850) to determine the incidence of t-MDS/AML and associated risk factors. Between 1988 and 1992, all patients were assigned randomly to standard chemotherapy with doxorubicin (dox), vincristine (VCR), cyclophosphamide (CPM), and dactinomycin (DACT) (Regimen A: n=262) or experimental therapy consisting of these four drugs in alternation with Ifosfamide (I) and etoposide (E) (Regimen B: n=256). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to Regimen C (n=60). Cumulative therapeutic exposures were: Regimen A: CPM:20.4 g/2, dox:375 mg/m2; Regimen B: CPM:9.6 g/m2, dox:375 mg/2, E:5 g/m2, I:90 mg/2; Regimen C: CPM:17.6 g/m2, dox:450 mg/m2, E:5 g/m2, I:140 g/m2. Results: Median age at diagnosis (dx) was 12.0 yr. Eleven patients developed t-MDS/AML [Regimen A (n=3), Regimen B (n=2), Regimen C (n=6)] at a median of 3 yr., with a cumulative incidence of 2% at 5 years. Magnitude of risk by regimen is shown in the Table. Multiple regression analysis revealed that Regimen C (RR=15.9, 95% CI, 3.8–65.8), but not Regimen B (RR=0.6, 95% CI, 0.1–3.7) was associated with an increased risk of developing t-MDS/t-AML when compared with Regimen A. Age at diagnosis, gender, and use of radiation therapy for local control did not increase the risk of t-MDS/AML. Conclusions: The risk of t-MDS/AML after Ewing’s sarcoma is not increased after exposure to ifosfamide at a dose of 90 g/m2, or etoposide at 5 g/m2, when compared to those not exposed to ifosfamide or etoposide, but that the risk increases dramatically after exposure to ifosfamide at cumulative doses of 140 g/m2. No significant financial relationships to disclose.
Daily dose of perifosine less toxic than weekly and active in patients with hepatocellular carcinoma (HCC)
Authors: L. T. Campos, J. Stephenson, F. Swan, D. Richards, R. Birch, I. Henderson
Journal: Journal of Clinical Oncology (2007)

15072 Background: P is a novel oral alkylphosphocholine with effects on multiple signal transduction pathways including Akt, MAPK and JNK. Unresectable HCC has a dismal prognosis. In the only large randomized trial, the response rate to single agent chemotherapy was &lt;3% and median progression free survival (PFS) was l0 weeks. In small series response rates up to 25% have been reported with combination regimens Methods: Patients (pts) were accrued to a broad phase 2 trial &amp; randomized to P, 50 mg daily or 1200 mg weekly, between 3/05 and 5/06, at which time the protocol was amended to P 100 mg daily or 900 mg weekly because the daily dose was so non-toxic and the weekly dose too toxic. The amended protocol is still open. A Simon two-stage design was used for each cancer, and HCC is one of several tumor types that have fulfilled criteria for expansion into the second stage. Results: Prior to protocol amendment 241 pts, including 13 with HCC, were entered. The daily dose was very well tolerated; 70% had no or only grade 1 toxicity. The principle toxicities are gastrointestinal and fatigue. (See table ) The weekly dose was significantly more toxic. The median age of the HCC pts was 64(range 22 - 80); 9 patients were male and the median ECOG performance status was 1, range 0–2. Eight had no prior chemotherapy. Eleven were evaluable for response, and 1 without prior chemotherapy who was treated on the 50 mg daily dose had a partial response lasting for 9 months. In addition, 5 (4 on the 50 mg daily dose) were progression free for &gt; 6 months. This included 2 with 2 and 3 prior regimens. Conclusions: This study demonstrated that perifosine has very little toxicity when administered at a dose of 50 mg daily and is active in HCC as well as other cancers [Table: see text] No significant financial relationships to disclose.
A multicenter phase II study of gemcitabine (GEM) in patients with unresectable biliary tract cancer
Authors: A. Funakoshi, T. Okusaka, H. Ishii, K. Yamao, S. Ohkawa, H. Saito, S. Saito, T. Tsuyuguchi
Journal: Journal of Clinical Oncology (2005)

4145 Background: Biliary tract cancer is one of the most malignant tumors, progresses in a short time period, and has a bleak prognosis. Moreover, early detection is difficult, and there is no standard therapy for patients with unresectable biliary tract cancer. The primary objectives of this study were to evaluate the response rate and toxicities of GEM in patients with unresectable biliary tract cancer; secondary objectives included response duration, progression-free survival, and overall survival. Methods: Patients with histologically or cytologically confirmed biliary tract cancer and measurable lesions were enrolled. GEM 1000 mg/m2 was administered once weekly for 3 consecutive weeks followed by a week of rest. This 4-week schedule was then repeated. Results: From December 2001 to April 2004, 40 patients with a median age of 61 (range, 33–73) were enrolled; the majority of patients had a PS of 0 (60.0%), and primary lesions were extra hepatic bile duct (30.0%), gallbladder (55.0%), and ampulla of Vater (15.0%). All 40 patients were evaluable for efficacy and safety. Seven patients had partial responses for an overall response rate of 17.5% (95% CI, 7.3%–32.8%); 15 patients had stable disease; 17 had progressive disease; and 1 was not evaluable. The median response duration was 9.4 months (range, 2.6–9.4; 95% CI, 3.8–9.4); the median progression-free survival was 2.6 months (range, 0.7–13.5; 95% CI, 1.7–3.8). The median survival was 7.6 months (range, 1.6–27.1+; 95% CI, 5.4–9.3), and the 1-year survival rate was 25.0%. The most common grade 3/4 hematologic toxicities were neutropenia (30.0% of patients) and ALT elevation (15.0%). The most common grade 3/4 nonhematologic toxicities were constipation (7.5%), vomiting (7.5%), and anorexia (7.5%). For 34 patients (85.0%), GEM was received on an outpatient basis. Conclusions: GEM monotherapy had good survival benefits and manageable toxicities. The safety profile was not different between patients with biliary drainage or a stent for jaundice and those without jaundice. GEM is also likely to contribute to improvement of patients’ quality of life based on its ease of administration. No significant financial relationships to disclose.
Hypofractionated accelerated high-dose radiotherapy (RT) in non-small cell lung cancer (NSCLC)
Authors: S. M. Brennan, D. Fitzpatrick, J. Armstrong, A. McElroy, M. Dunne, C. O Shea, P. Thirion
Journal: Journal of Clinical Oncology (2008)

7527 Background: Dose escalation and RT intensification may improve local control in NSCLC but may potentially increase late toxicity. We postulated that accelerated hypofractionated RT is safe and efficacious with use of 3D-CRT and application of strict dose volume constraints (DVC). Methods: 50 patients with stage I–III medically inoperable/unresectable NSCLC, with weight loss less than 10% and KPS >70% were enrolled on a phase 1/11 clinical trial (ICORG 99–09) with a schedule of 72 Gy in 24 fractions, once daily, five fractions per week, over 32 days. Median age = 65 years (Range: 45–82 yrs). 39 patients were male and 11 female. 31 patients had induction chemotherapy. No elective lymph node irradiation was used. Primary endpoints were acute and late esophageal (RTOG/EORTC scale) and pulmonary toxicity (SWOG). Secondary endpoints were response rate at 3 months, time to tumor progression (TTP), time to tumor local progression (TTLP), time to distant progression (TTDP), progression-free survival (PFS) and overall survival (OS). Results: 45 patients were treated with median f/u =11 months (range 3–73 mos). Acute toxicity was as follows: acute pneumonitis (20 pts: Grade (Gr) 1=19 pts, Gr2=1 pt); acute esophagitis (20 pts: Gr1=14pts, Gr2=3 pts, Gr3=3 pts) with one 4 day treatment interruption. 12 pts had late pneumonitis (Gr1=10 pts, Gr2=2 pts). A previous analysis presented at ASCO 2004 reported 2 pts with Gr 5 late esophagitis. Therefore, we introduced an additional esophageal DVC where <1 cm of circumferential esophagus was within the 98% isodose. Since then 8 patients were treated with no grade 5 toxicity and Gr1 = 1pt, Gr2 = 1pt, Gr3=1pt, with median f/u = 9 mos. Tumor response rate at 3 mos: (18% CR, 29% PR, 15% SD, 17% PD and 20 % non-evaluable). Median TTP = 12 mos, median TTLP =21 mos, and median TTDP = 11 mos. 1 yr PFS=81%, 3 yr PFS=28%. Median OS=17 mos with 1 yr OS=81%, 3 yr OS=25%. Conclusions: The toxicity profile is favorable apart from initial unexpected esophageal late toxicity. We continue to evaluate the safety of our esophageal DVC. The median survival and TTLP results are encouraging as 40% pts had Stage III disease. No significant financial relationships to disclose.
Gefitinib and erlotinib: Same or different tyrosine kinase inhibitors (TKIs)?
Authors: F. Roila, M. C. Garassino, S. Cobelli, M. Broggini, P. Sburlati, A. Mancuso, M. Dimaiuta, O. Martelli, G. Farina, V. Torri
Journal: Journal of Clinical Oncology (2008)

14662 Background: The survival benefit of TKIs in advanced non small lung cancer (NSCLC) is modest and gefitinib and erlotinib are usually considered drugs with similar efficacy. Methods: We performed a pooled analysis in order to assess the efficacy of these drugs alone or in combination.An electronic search focused on randomized controlled trials assessing efficacy or activity of TKIs alone or associated with chemotherapy in NSCLC was performed. A pooled analysis was accomplished and Hazard Ratio (HR) with 95% confidence interval was derived. Results: Only six papers were considered for analysis. Overall, there was a 3% (HR: 0.97, 95% CI 0.91–1.03) mortality reduction and a 10% reduction in event rate (HR: 0.90, 95%CI 0.85–0.95). Results differed when analysing II line therapies vs. I line therapies, in which TKI was added to chemotherapy. In first line chemotherapy there was a consistent lack of effect, while in II line there was a 18% reduction in mortality (HR: 0.82, 95%CI 0.73–0.92) and a 24% reduction in event rate (HR: 0.76, 95%CI 0.68–0.83) with a greater effect showed for erlotinib therapy (test for heterogeneity between studies, p= 0.04 and 0.007 for OS and PFS respectively). Conclusions: From our results erlotinib and gefitinib seem to be drugs with different efficacy; although structurally related and with the same ability to interfere with the EGFR- mediated cascade, erlotinib and gefitinib have some pharmacological differences which could account for the observed differences in activity. Erlotinib is for example less susceptible to the metabolism mediated by cytochrome P450 3A than gefitinib and this could account for the lower clearance (compared to gefitinb) observed for erlotinib. In addition, erlotinib inhibits the activity of wild type EGFR at lower concentrations than those necessary with gefitinib. A combination of higher circulating levels of erlotinib plus a stronger potency in inhibiting wild type target activity could at least in part explain the differences. No significant financial relationships to disclose.
Is intravenous (iv) IL2 superior to subcutaneous (sc) IL2 in good prognosis patients (pts) with metastatic renal cell carcinoma (MRCC) receiving a combination of IL2 and alpha interferon (IFN)? Results of the prospective randomized PERCY Duo trial
Authors: S. Negrier, D. Perol, A. Ravaud, J. O. Bay, S. Oudard, P. Fargeot, R. Delva, G. Deplanque, G. Gravis, B. Escudier
Journal: Journal of Clinical Oncology (2006)

4536 Background: Pts with a single metastatic site are more likely to benefit from an IL2 and IFN combination (Negrier NEJM 1998). The French Immunotherapy Intergroup designed a multicenter trial to assess the potential benefit of iv over sc IL2 in IL2+IFN combination in this subgroup. Methods: Untreated pts, Karnofsky score ≥ 90 and a single metastatic site were randomized into this 2 arm trial. Pts received continuous IL2 infusion (18 million IU/m 2 /d) (arm A), or sc IL2 injections (9 or 18 million IU) twice daily (arm B). IFN was given sc (6 million IU) 3d/week in both arms. Tumor responses (OMS criteria) were assessed at weeks 12 and 27. The primary endpoint was overall survival (OS), with an expected difference of 15% at 4 yrs in favor of iv IL2. The planned sample size was 220 to have 80% power at 5% significance level with a one-sided test. One intent-to-treat analysis was performed and survivals were compared using log-rank tests. Results: From January 00 to January 05, 80 and 75 pts were randomized to arms A and B respectively. Enrollment was stopped early due to low accrual; analysis was performed at 40-month median follow up. Patient characteristics were well balanced between groups. Median age was 55, 82% pts were male, 68% had lung metastases, and 37% had more than 1 year from renal tumor to metastases. No toxic death occurred, gr 3/4 vomiting, rise in creatinine level, hypotension and neurologic toxicity were significantly higher in arm A. Response rates were 17.9 vs 21.3%, in arms A and B, respectively. Progression-free survivals were not significantly different (P: 0.285). The difference in OS was not significant: median 37.7 months [95%CI: 28.2–58.4] with iv IL2 vs. 26.3 [95%CI: 24.5–34.2] with sc IL2 (P: 0.127). Conclusions: Iv IL2 combined with IFN confers no significant advantage over a sc IL2 combination in selected pts with good prognosis MRCC. Since some toxicities were significantly more frequent with iv IL2, the use of this combination cannot be recommended. Because of premature stop, the trend in favor of iv IL2 should encourage further studies before final conclusions can be drawn. [Table: see text]
Radical surgery is not necessary following neoadjuvant chemotherapy in stage III-IV resectable, non-laryngeal head and neck cancer (NLHNC)
Authors: J. A. Shultz, C. R. Pameijer, J. Ellenhorn, S. Shibata, N. Vora, E. Maghami, I. B. Paz
Journal: Journal of Clinical Oncology (2007)

16501 Background: Traditionally, following neoadjuvant chemotherapy (NC), head and neck surgeons have insisted in performing radical surgery regardless of the response to NC. This prospective study evaluates the results of conservative surgery following NC in resectable stage III-IV non-laryngeal head and neck cancer (NLHNC). Methods: Between 1993 and 2003, 70 patients with NLHNC were treated with one of the following NC: Cisplatin and 5FU (17.1%); Cisplatin, 5FU, Leucovorin, and Taxotere (58.6%); Cisplatin, 5FU, and Taxol (24.3%). After three courses of NC, patients were reevaluated to determine the need for local therapy. Local excision or biopsy was performed for patients with near-complete pathological response (n-CPR) or patients with a complete pathological response (CPR). Radical surgery was reserved for patients with partial response (PPR). All patients received radiation to the primary and neck. Results: The median follow up was 35 months, median disease-free survival was 33.4 months and 3-year overall survival was 71.4% for the entire group. Thirty-five patients (50.0%) had a complete pathological response (CPR), 11 (15.7%) had a complete clinical response (CCR) and no pathological staging, 5 patients (7.1%) had a n-CPR, and 19 patients (27.1%) had a partial pathological response (PPR). Primary surgery is shown in the following table : At the time of the last follow up, 1/35 (2.9%) patients with CPR had a local recurrence (LR) at the primary and 5/11 (45.5%) patients with CCR and no pathological staging had a LR; in 3/6 (50%) patients with LR the primary was controlled with salvage surgery. Seven of eleven (63.6%) patients with PPR had a LR, only one achieved local control with salvage surgery. Conclusions: Complete pathological response at the primary site is a good predictor of long term local control in NLHNC. Radical surgery, is not necessary in non-laryngeal head and neck cancers following a complete pathological response at the primary site. [Table: see text] No significant financial relationships to disclose.
Doppler ultrasonography with perfusion software and contrast agent injection as a tool for early evaluation of metastatic renal cancers treated with the Raf kinase and VEGFR inhibitor: A prospective study
Authors: M. Lamuraglia, N. Lassau, L. Chami, S. Jaziri, B. Schwartz, J. Leclere, B. Escudier
Journal: Journal of Clinical Oncology (2005)

3069 Background: BAY 43–9006 (BAY) is a novel Raf kinase and VEGFR inhibitor currently under investigation in phase III trials for the treatment of metastatic renal cancer (MRCC). BAY appears to have strong anti-angiogenic activity. The objective of this study is to evaluate Doppler Ultrasonography with perfusion software (Vascular Recognition Imaging, Toshiba) and contrast agent injection (Sonovue - Bracco) (DUSVRI) as a predictor of tumor response to this new treatment and of progression-free survival (PFS). Methods: Tumor vascularization in accessible targets was prospectively studied with DUSVRI, through a double-blind placebo controlled phase III study in MRCC. Examinations were performed with an Aplio sonograph (Toshiba) at baseline, and after 3 and 6 weeks on BAY (or the placebo) in patients with tumor targets accessible to US. The percentage of contrast uptake (Sonovue, Bracco) was evaluated in each tumor by two radiologists. Results were compared to CT scan studies at 6 weeks and to PFS, and will be analyzed after unblinding. Results: 30 patients have been enrolled and a total of 84 examinations have been performed to date: 30 before randomization, 28 at 3 weeks and 25 at 6 weeks. Preliminary results show a decrease in tumor vascularization in 10 out of 28 patients at 3 weeks and in 10 out of 25 patients at 6 weeks. The final results concerning 30 patients will be presented and a correlation with the CT-scan response at 6 weeks. Conclusions: DUSVRI is a new cost-effective and simple non invasive imaging technique. Its effectiveness in predicting the efficacy of BAY will be presented. No significant financial relationships to disclose.
Phase I clinical trial of CX-3543, a pro-apoptotic antitumor agent
Authors: R. F. Marschke, A. D. Ricart, D. D. Von Hoff, J. K. Lim, K. Papadopoulos
Journal: Journal of Clinical Oncology (2006)

3082 Background: CX-3543 is a novel small molecule specifically designed to target three dimensional nucleic acid motifs, and thus induce apoptosis in cancer cells. Preclinically, CX-3543 demonstrated potency in suppressing xenograft tumor growth with a broad therapeutic window. The objectives of this phase I study are: to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs), to establish the pharmacokinetics (PKs), and to determine the recommended dose for further clinical development of CX-3543. Methods: Eligible patients with advanced solid tumors or lymphomas whose tumors progressed on standard therapy or for whom there are no standard therapies receive CX-3543 in successive dose cohorts at: 10, 20, 40, 80 and 160 mg/m 2 . Dosing is by one hour intravenous infusion daily for five consecutive days repeated on a three week cycle. Therapy is continued until the patient shows signs of intolerance to CX-3543 or evidence of advancing disease. Response by RECIST criteria is determined after every 2 cycles. Results: Ten patients with solid tumors (3–4 per cohort) have received intravenous CX-3543. Doses have been well tolerated. Seven grade 3 adverse events have been reported during the study, but none of these are related to CX-3543. To date no objective responses have been observed. One patient with advanced refractory prostate cancer has stable disease of longer than 4 months duration. CX-3543 has demonstrated good linearity in PK parameters between the dose cohorts with a terminal half life of approximately 12 hours following the first dose. Conclusions: To date, CX-3543 has shown no drug related toxicity and has predictable PKs. No DLTs have yet been observed, and the MTD remains to be defined in this Phase I study. Further enrollment to the planned dose escalation cohorts is ongoing. [Table: see text]