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Background Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tiss...

Goosegrass control options in bermudagrass are limited. Topramezone is one option that offers excellent control of mature goosegrass, but application to bermudagrass results in unacceptable symptoms of bleaching and necrosis typical of hydroxyphenylpyruvate dioxygenase inhibitors. Previous research has shown that adding chelated iron reduced the phytotoxicity of topramezone without reducing the efficacy of the herbicide, resulting in safening when applied to bermudagrass. Our objective was to examine additional iron sources to determine whether similar safening effects occur with other sources. Field trials were conducted in the summers of 2016 to 2018 (Auburn University). Mixtures of topramezone and methylated seed oil were combined with six different commercial iron sources, including sodium ferric ethylenediamine di-o-hydroxyphenyl-acetate (FeEDDHA), ferrous diethylenetriamine pentaacetic acid (FeDTPA), iron citrate, FeSO4, and a combination of iron oxide/sucrate/sulfate, some of which contained nitrogen. Bermudagrass necrosis and bleaching symptoms were visually rated on a 0% to 100% scale. Reflectance (normalized difference vegetation index) and clipping yield measurements were also collected. Application of FeDTPA and FeSO4 reduced symptoms of bleaching and necrosis when applied with topramezone. Other treatments that contained nitrogen did not reduce injury but did reduce bermudagrass recovery time following the appearance of necrosis. Inclusion of small amounts of nitrogen often negated the safening effects of FeSO4. The iron oxide/sucrate/sulfate product had no effect on bleaching or necrosis. Data suggest that the iron source had a differential effect on bleaching and necrosis reduction when applied in combination with topramezone to bermudagrass. Overall, FeSO4 and FeDTPA safened topramezone the most on bermudagrass.

POST goosegrass and other grassy weed control in bermudagrass is problematic. Fewer herbicides that can control goosegrass are available due to regulatory pressure and herbicide resistance. Alternative herbicide options that offer effective control are needed. Previous research demonstrates that topramezone controls goosegrass, crabgrass, and other weed species; however, injury to bermudagrass may be unacceptable. The objective of this research was to evaluate the safening potential of topramezone combinations with different additives on bermudagrass. Field trials were conducted at Auburn University during summer and fall from 2015 to 2018 and 2017 to 2018, respectively. Treatments included topramezone mixtures and methylated seed oil applied in combination with five different additives: triclopyr, green turf pigment, green turf paint, ammonium sulfate, and chelated iron. Bermudagrass bleaching and necrosis symptoms were visually rated. Normalized-difference vegetative index measurements and clipping yield data were also collected. Topramezone plus chelated iron, as well as topramezone plus triclopyr, reduced bleaching potential the best; however, the combination of topramezone plus triclopyr resulted in necrosis that outweighed reductions in bleaching. Masking agents such as green turf paint and green turf pigment were ineffective in reducing injury when applied with topramezone. The combination of topramezone plus ammonium sulfate should be avoided because of the high level of necrosis. Topramezone-associated bleaching symptoms were transient and lasted 7 to 14 d on average. Findings from this research suggest that chelated iron added to topramezone and methylated seed oil mixtures acted as a safener on bermudagrass.

PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.

5519 Background: Lower responses to chemotherapy and the unique molecular profile of LGSO led to the adoption of MEK-inhibitors for this disease. Updated analysis from the MILO/ENGOT-ov11 phase III study of binimetinib vs PCC in recurrent LGSOC showed response rate of 24% in those treated with binimetinib (JCO, 2020; NCT01849874). Here we present results of the post-hoc tumor tissue biomarker analysis performed with MILO/ENGOT-ov11. Methods: Mutational/copy number analysis was performed via Foundation Medicine on archival tissue obtained prior to randomization. Unbiased univariate analysis was used to test association between mutation status and outcomes in binimetinib and PCC treated patients. Outcomes examined were progression free survival (PFS), binary response by local RECIST 1.1 (complete or partial response [CR/PR] vs. stable [SD] or progressive disease [PD]), and ordinal response. Kaplan-Meier was used to estimate PFS. Cox regression, binary logistic regression, and ordinal logistic regression were used to examine relationship between mutation status and outcomes. Results: MILO/ENGOT-OV11 enrolled 341 patients from June, 2013 to April, 2016. Patients were randomized 2:1 to binimetinib or PCC. Based on January 1, 2020 data cut-off the data is as-is, amongst those patients treated with binimetinib with molecular results available, PFS data is available for 144 and response rate (RR) data for 135. There were 47 mutations detected in ≥5% of patients, most commonly KRAS (33%). Patients harboring a KRAS mutation had 3.4 times the odds of responding to treatment with binimetinib as patients without KRAS mutation (95% CI 1.57,7.67; p-value 0.002). There was no difference in effect of KRAS G12V mutation vs other KRAS mutation on PFS (PFS HR 1.06; 95% CI:0.53, 2.12; p value 0.9). In the 135 patients with binimetinib RR data, other MAPK mutations were identified as follows; NRAS in 11(8.1%), BRAFV600E in 8(5.9%), RAF1 in 2 (1.5%), NF1 in 7 (5.2%). In patients with MAPK mutation (as defined above) the RR was 41% vs 13% in those without MAPK mutation. PFS was significantly better in patients treated with binimetinib harboring MAPK mutation vs those without (HR 0.5; 95% CI 0.31, 0.79; p = 0.003). In patients treated with PCC there was a nonsignificant trend towards improved PFS in those with MAPK mutation vs those without (HR 0.82; 95% CI 0.43,1.59; p = 0.6). A test for interaction between treatment and MAPK pathway was not significant by Cox regression model (p = 0.32). Conclusions: While this hypothesis generating analysis is limited by multiple testing, higher response rates and longer PFS were seen in those patients with LGSOC treated with binimetinib who harbored MAPK mutations, most commonly in KRAS. Somatic tumor testing should be routinely performed in patients with recurrent LGSOC to aid in clinical decision making. Clinical trial information: NCT01849874.

In clinical trials with time-to-event outcomes, it is common to estimate the marginal hazard ratio from the proportional hazards model, even when the proportional hazards assumption is not valid. This is unavoidable from the perspective that the estimator must be specified a priori if probability statements about treatment effect estimates are desired. Marginal hazard ratio estimates under non-proportional hazards are still useful, as they can be considered to be average treatment effect estimates over the support of the data. However, as many have shown, under non-proportional hazard, the 'usual' unweighted marginal hazard ratio estimate is a function of the censoring distribution, which is not normally considered to be scientifically relevant when describing the treatment effect. In addition, in many practical settings, the censoring distribution is only conditionally independent (e.g., differing across treatment arms), which further complicates the interpretation. In this paper, we investigate an estimator of the hazard ratio that removes the influence of censoring and propose a consistent robust variance estimator. We compare the coverage probability of the estimator to both the usual Cox model estimator and an estimator proposed by Xu and O'Quigley (2000) when censoring is independent of the covariate. The new estimator should be used for inference that does not depend on the censoring distribution. It is particularly relevant to adaptive clinical trials where, by design, censoring distributions differ across treatment arms.

Purpose Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity. Patients and Methods Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m2/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS). Results Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%). Conclusion To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.

Purpose Efaproxiral (RSR13) reduces hemoglobin oxygen–binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non–small-cell lung cancer (NSCLC). Patients and Methods Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10. Results Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%). Conclusion Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.

Purpose To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT). Patients and Methods Patients with brain metastases from solid tumors and a Karnofsky performance score of ≥ 70 were randomly assigned to receive WBRT with supplemental oxygen and either efaproxiral at 75 or 100 mg/kg (efaproxiral arm) or no efaproxiral (control arm). The primary end point was survival. Results The study consisted of 515 eligible patients (efaproxiral arm, n = 265; control arm, n = 250). The median survival time (MST) was 5.4 months for the efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] = 0.87; P = .16). For the subgroup of patients with non–small-cell lung cancer (NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR = 0.82; P = .07). Cox multiple regression analysis demonstrated a significant reduction in the risk of death for the efaproxiral arm in both primary populations. Further analysis indicated that the benefit may be restricted to the subgroup of patients with breast cancer. Response rates (radiographic complete response plus partial response) improved by 7% (P = .10) and 13% (P = .01) for all patients and for NSCLC and breast cancer patients in the efaproxiral arm, respectively. The most common severe adverse event in patients treated with efaproxiral was hypoxemia, which was reversible and effectively managed with supplemental oxygen in most patients. Conclusion The addition of efaproxiral, a noncytotoxic radiation sensitizer, to WBRT may improve response rates and survival in patients with brain metastases, particularly metastases from breast cancer. A confirmatory trial for breast cancer patients has been initiated.

Purpose: To determine the prognostic factors for radiographic response and its prognostic value for subsequent survival in patients undergoing whole-brain radiotherapy (WBRT) for brain metastases. Methods and Materials: Five hundred fifteen eligible patients were randomized in a phase III trial evaluating WBRT and supplemental oxygen with or without efaproxiral, an allosteric modifier of hemoglobin that reduces hemoglobin oxygen-binding affinity and enhances tumor oxygenation, potentially increasing tumor radiosensitivity. Brain images were obtained at baseline and at scheduled follow-up visits after WBRT. Landmark analysis was used to assess the ability of response at selected time points to predict subsequent survival. Logistic regression was used to assess determinants of response at 3 months. Results: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit ( p = 0.02). Response at 3 and 6 months was a significant prognostic factor for longer subsequent survival. Conclusions: The 3-month scan is a valuable prognostic factor for subsequent survival in patients with brain metastases treated with WBRT. Patients in the efaproxiral arm had a higher response rate at 3 and 6 months than those in the control arm.

TPS5610 Background: Low-grade serous (LGS) carcinomas of the ovary, fallopian tube and primary peritoneum are a unique subset of serous carcinomas for which current therapies (chemotherapy, hormona...

8054 Background: Pralatrexate (FOLOTYN) is a targeted antifolate designed for preferential uptake and accumulation in tumor cells, due to high affinity for reduced folate carrier and efficient poly...

Abstract 3420 Poster Board III-308 Background Stem cell transplant (SCT) may be offered as a curative approach in patients with chemotherapy-sensitive peripheral T-cell lymphoma (PTCL). Thus, new agents with the ability to induce a response for relapsed or refractory patients are important to identify. This analysis evaluated SCT use before or after pralatrexate, a new anti-folate, as monotherapy in the PROPEL study. Methods Patients with relapsed or refractory PTCL received pralatrexate 30 mg/m2 by IV push once weekly for 6 weeks in 7-week cycles with vitamin B12 and folic acid supplementation in PROPEL. Eligibility criteria included histologic confirmation of PTCL by central review, disease progression after ≥ 1 prior treatment, and ECOG performance status £ 2. Response was assessed centrally using the International Workshop Criteria. Patients who had received prior allogeneic SCT were not permitted to enroll. Patients with prior autologous SCT were eligible if they had not relapsed within 75 days of SCT. There were no restrictions on SCT after completing study treatment. Subsequent post-pralatrexate therapies were recorded during follow up until patient death, loss to follow-up, or data cutoff. Results One-hundred and nine patients in the PROPEL trial were evaluable for response. Eighteen (16%) had received autologous SCT previously, including 8 (7%) patients for whom SCT was the most recent therapy prior to study enrollment. The overall response rate (ORR: complete response [CR/CRu] or partial response [PR]) was 33% (6/18), including 2 CRs, for patients with a prior autologous SCT at any time prior to receiving pralatrexate and 63% (5/8), including 2 CRs, for those patients whose most recent therapy was autologous SCT. Patients were followed from initiation of pralatrexate for a median of 10.5 months (range, 1.0-24.0). Of the 109 patients who were evaluable for response, 6 (6%) patients went on to SCT (2 autologous SCT, 4 allogeneic SCT) as their initial subsequent therapy after responding to pralatrexate according to investigator assessment of response. Four of these patients were still in response by central review at the time they started SCT. At the time of data cutoff, no additional therapy was administered to any of these 4 patients post SCT. The other 2 patients had PRs by investigator review and progressive disease by central review at the time SCT was started; neither of these patients had additional therapy documented after SCT. All 6 patients were alive at the time of last contact. Conclusions The PROPEL trial showed that pralatrexate as a single agent had activity, including CRs, in patients who relapsed following an autologous SCT. The PROPEL trial also demonstrated that patients with relapsed or refractory PTCL can proceed to subsequent SCT after achieving a response with pralatrexate, permitting these patients a transplant option and potential cure. Disclosures Pro: Allos Therapeutics, Inc.: Research Funding. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Boyd:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment.

Abstract 1681 Poster Board I-707 Background The rationally designed antifolate, pralatrexate, has high affinity for reduced folate carrier-1 (RFC-1) and was designed to be retained longer within cancer cells due to efficient polyglutamation by folylpolyglutamyl synthetase (FPGS). Prophylactic vitamin supplementation with folic acid and vitamin B12 is often used by physicians to minimize toxicities seen with antifolate chemotherapy (Scagliotti GV, JCO 2003; 21:1556). Nutritional status is a concern for cancer patients in general, and particularly for patients with aggressive disease that have been treated previously. In the PROPEL study, a pivotal international multi-center Phase 2 study of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), patients were treated with pralatrexate and received folic acid and vitamin B12 supplementation. Patients in PROPEL had been treated with a median of three prior regimens, and an overall response rate of 28% by independent central review was observed. The most common grade 3-4 toxicities were thrombocytopenia (32%) and mucositis (22%). This report includes analyses of baseline MMA, Hcy, and RBC folate levels and their association with thrombocytopenia or mucositis in the PROPEL trial. Methods Patients received pralatrexate 30 mg/m2 IV weekly for 6 weeks in 7-week cycles and supplementation with vitamin B12 (1 mg IM q8-10 wks) and folic acid (1.0-1.25 mg PO daily). Eligibility criteria included histologically confirmed PTCL, disease progression after ≥ 1 prior treatment, and ECOG performance status £ 2. MMA, Hcy and RBC folate levels were measured at baseline, prior to vitamin initiation. A linear model was used to estimate the relationship (slope) between each of these baseline values and the maximum grade of mucositis and thrombocytopenia. Results Of the 115 patients enrolled, 111 were evaluable for safety and 109 were evaluable for response. Eighty-nine had baseline MMA levels, 91 had baseline Hcy levels, and 75 had baseline RBC folate levels before initiation of vitamin supplementation. Baseline values are summarized by the highest grade of thrombocytopenia or mucositis in the Table. The linear relationship between maximum mucositis grade on study (0 vs 1-2 vs 3-4) and baseline MMA was statistically significant (slope estimate = 43.3 nmol/L, p = 0.039). In addition, there was a trend for increasing MMA and increasing severity of thrombocytopenia that did not meet statistical significance (slope estimate = 17.6 μmol/L, p = 0.267). No other significant relationships were noted. Conclusions In the subset of relapsed or refractory PTCL patients tested for MMA levels in the PROPEL study, higher levels of baseline MMA were associated with increased severity of mucositis. There was an association between MMA and severity of thrombocytopenia that did not reach statistical significance. RBC folate and Hcy were not predictive of the severity of mucositis and thrombocytopenia in this analysis. Because patients with relapsed or refractory PTCL may have poor nutritional status, all patients treated with pralatrexate, including those with elevated MMA, should be supplemented with vitamins. Additional studies may be warranted to define the relationship between MMA levels and the development of mucositis and thrombocytopenia among patients treated with pralatrexate. Disclosures Pro: Allos Therapeutics, Inc: Research Funding. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Boyd:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment.

Background: Pralatrexate (PDX) is a novel targeted antifolate that is designed to accumulate preferentially in cancer cells. Pralatrexate selectively enters cells expressing RFC-1, a protein that is over expressed on cancer cells compared to normal cells. Once inside cancer cells, pralatrexate is very efficiently polyglutamated, which leads to high intracellular drug retention. The PROPEL trial, a pivotal Phase 2, single-arm, nonrandomized, open-label, multi-center study is the largest prospective study in pts with PTCL. PROPEL was designed to evaluate the safety and efficacy of pts with relapsed or refractory PTCL. Methods : Pts receive 30 mg/m2 of pralatrexate intravenously (IV) weekly for 6 of 7 weeks in addition to vitamin B12 and folic acid supplementation. The primary endpoint is objective response rate (ORR), with secondary endpoints of response duration, progression-free survival (PFS), and overall survival (OS). Eligibility criteria included histologically/cytologically confirmed PTCL, documented disease progression (PD) after □ 1 prior treatment, and Eastern Cooperative Oncology Group performance status (ECOG PS) □ 2. Response was assessed by independent central review using the International Workshop Criteria (IWC). Safety was monitored at 3 preplanned time-points during the study by an external data safety monitoring committee (DSMB). Results : This study is fully accrued. From Aug 2006 to Apr 2008, 115 pts were enrolled, 107 of whom are considered evaluable per the protocol for response (those who received at least 1 dose of pralatrexate whose diagnosis of PTCL was confirmed by independent review). Interim data are available at this time for the first 65 evaluable pts, which includes 41 males (63%) and 24 females (37%). These pts were heavily pre-treated and had failed a median of 3 prior regimens. Ten (15%) had previously undergone an autologous stem cell transplant. The majority (34, 52%) of pts had PTCL not-otherwise specified (PTCL-NOS), with most others having anaplastic large cell lymphoma (10, 15%; 3 AKL+, 7 ALK−), transformed mycosis fungoides (7, 11%), or angioimmunoblastic T-cell lymphoma (7, 11%). Nineteen of 65 patients responded (29%). See the table below for complete efficacy results per independent central oncology review. Seven pts of the 19 responding pts (37% of responders) had a best response of CR. Four pts had insufficient response data, and response could not be assessed for 9 pts due to discontinuation prior to cycle 1 completion, although these pts are counted in the denominator for the ORR. Efficacy Results According to Central Review | Endpoint | Value | Pralatrexate (N=65) n(%) | |:----------------------:| ----------------------------------- | ------------------------ | | Total # responders/ORR | CR/PR | 19 (29) | | Best Response | CR | 7 (11) | | | PR | 12 (18) | | | SD | 16 (25) | | | PD | 17 (26) | | | Insufficient data | 4 (6) | | | Discontinuation prior to assessment | 9 (14) | Of the 19 responders, 17 pts had evaluation by positron emission topography (PET) scan: 8 pts were deemed to have a CR and 9 had a PR. ORR as assessed by study investigators showed that 45% (n=29) of pts experienced either a CR or PR. Of the 65 pts, 14 (22%) received pralatrexate for □ 6 months. The most frequently reported Grade (Gr) 3–4 AEs considered to be related to pralatrexate were thrombocytopenia (20 pts [31%]), mucositis (9 pts [14%]), anemia (8 pts [12%]), and neutropenia (7 pts [11%]). Conclusion : To our knowledge, this represents the largest prospective study conducted in pts with relapsed or refractory PTCL. The results demonstrate that pralatrexate exhibits substantial activity, including CRs, in pts with heavily pre-treated PTCL. This trial is now fully accrued and study results on the entire population will be presented at the meeting.

1561 Background: 538 patients with brain metastases from selected solid tumors were randomized in a study of standard WBRT (30 Gy in 10 fractions) and supplemental oxygen with or without the radiation sensitizer RSR13 (efaproxiral) (Control n=267, RSR13 n=271). A non-significant improvement in MST was seen in favor of the RSR13 arm when results were analyzed by undajusted log-rank. The study showed a survival advantage for RSR13-treated patients versus controls after adjusting for imbalances in prognostic factors (Cox multiple regression) with the patients with breast cancer deriving the largest benefit from RSR13. Since a clear PK/Pharmacodynamic (PK = RSR13 concentration in RBCs and Pharmacodynamic = p50 shift) correlation had been established for RSR13 in previous studies, PK analyses were incorporated in the design of the present study. Methods: Blood samples were drawn for RSR13 PK analyses on Day 1 of RSR13 and at least once during the second week of RSR13 therapy. 188 patients had at least 2 PK det...