End Of Treatment Cycle Research Articles

Oral self-management of palbociclib using mobile technology: Findings from a nurse-led randomized controlled trial

ObjectivesTest the feasibility and effectiveness of a text message reminder intervention for the self-management of oral anticancer medication in patients with metastatic breast cancer. MethodsForty-three females initiating treatment with palbociclib participated in a two-armed prospective randomized clinical trial. Participants were randomized into the control (N ​= ​21) and intervention groups (N ​= ​22) from January 2020 to January 2023. Survey responses were collected at three-time points; 1) at consent, 2)end of treatment cycles, and 3) at a follow-up clinic visit. Surveys included a demographic questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, post-study assessment, and the R-15 Participant Satisfaction Questionnaire. Nurse providers completed the Adaptation of Stamps Nurse Workload questionnaire. ResultsThe COVID-19 pandemic and regulatory decisions supporting other CDK4/6 medications negatively influence recruitment; thus, a small sample for each arm only detected large differences between the two arms regarding effectiveness. Feasibility analysis was not conducted due to insufficient data, but the participants frequently used their smartphones for text messaging. Although the survey data were limited, participants provided anecdotal information supporting the use of text messaging as a positive method to remind them to take their medication, have their labs drawn, and attend MD visits. Participants would have liked text messages at the exact time they took their medications as a simple reminder. ConclusionsGiven the importance of cancer treatments and the difficulties patients experience during these treatments, text messages using smartphones can actively improve patients' engagement and their ability to manage their treatment regimens.

Wearing-Off Effect Toward the End of Treatment Cycles in Patients With MS Receiving High-Efficacy Disease-Modifying Therapies: Data From Social Media Listening (P3-3.009)

<h3>Objective:</h3> To explore how various stakeholders (patients living with multiple sclerosis [PlwMS], caregivers [CGs], health care practitioners [HCPs], advocacy groups) describe symptoms, timing, coping strategies, and impact on quality of life (QoL) of the wearing-off effect (WOE) while receiving disease-modifying therapies (DMTs; natalizumab, ocrelizumab, ofatumumab, rituximab). <h3>Background:</h3> Symptoms such as fatigue, mobility issues, and physical pain toward the end of treatment cycles (WOE) have been reported in PlwMS receiving DMTs. Patients on social media report a QoL impact associated with WOE. <h3>Design/Methods:</h3> Publicly available posts related to WOE on social media, blogs, and forums were reviewed. WOE-specific posts authored in English by key stakeholders and posted between February 1, 2020 and February 16, 2022 were analyzed. Posts were identified through a specific search term–based funneling methodology. <h3>Results:</h3> We identified 43,834 posts related to broader MS and WOE; 730 conversations were WOE specific, with 725 authored by PlwMS or CGs. Of these 725 posts, 535 were related to experiencing WOE and 277/535 posts mentioned WOE-associated symptoms. The most commonly reported WOE durations were 2–4 weeks; fatigue was the most mentioned symptom, followed by mobility issues and physical pain. Treatment was specified in 374/535 posts; 9% of these mentioned a QoL impact, such as need for more downtime, interference with work, and difficulty walking. WOE coping strategies mentioned by patients included switching to other DMTs, reducing intervals between cycles, and taking steroids/other medications. WOE-related conversations by HCPs and advocacy groups were scarce (4 and 1 posts, respectively). <h3>Conclusions:</h3> Mentions of WOE by patients receiving DMTs and reports of WOE-related symptoms impacting QoL were common. Factors like differing DMT durations and numbers of patients receiving different DMTs make observations of social media conversations prone to an inherent bias. Further research regarding WOE and potential gaps between HCP and patient perceptions/awareness of WOE is needed. <b>Disclosure:</b> Mr. Clement has received personal compensation for serving as an employee of Novartis. Mr. Clement has stock in Roche. Joanne Fielding, 24833 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . The institution of Joanne Fielding, 24833 has received research support from BioEye. The institution of Joanne Fielding, 24833 has received research support from Equity Trustees. The institution of Joanne Fielding, 24833 has received research support from Macquarie Group Foundation. The institution of Joanne Fielding, 24833 has received research support from Genzyme. The institution of Joanne Fielding, 24833 has received research support from Biogen. The institution of Joanne Fielding, 24833 has received research support from Open Medicines Australia. The institution of Joanne Fielding, 24833 has received research support from EyeOnVision. Ms. Serceau has nothing to disclose. Ms. Robinson has nothing to disclose. Chinmay Deshpande has received personal compensation for serving as an employee of Novartis Pharmaceutical Corporation . Chinmay Deshpande has stock in Novartis Pharmaceutical Corporation .

Utilizing CLL-1 Positive Leukemia Stem Cells As a Marker of Early Treatment Response in Acute Myeloid Leukemia

Background: Current methods to evaluate therapeutic response in Acute Myeloid leukemia (AML) rely primarily on morphological evaluation of leukemia blasts in bone marrow at end of treatment cycles, with complete remission (CR) defined as less than 5% bone marrow blast counts without leukemic phenotype. Measurable residual disease (MRD) has been shown highly prognostic for outcome. MRD by molecular methods is limited to subgroup of patients with defined genetic mutations. MRD detection by Multicolor Flow Cytometry (MFC) is still being standardized. Leukemia stem cells (LSC) has been established as source of treatment resistance and disease recurrence in AML. In this study, we aim to analyze change in LSC during treatment using immunophenotypically defined markers and examine whether information gained from LSC analysis could provide additional insights into disease course and assist management of AML under routine clinical practice setting. Methods: We analyzed flow cytometry data from bone marrow aspirate (BMA) and/or peripheral blood (PB) in patients with AML (excluding acute promyelocytic leukemia) before and after treatment. "Leukemic blasts” were identified by morphology and Leukemia-associated Immunophenotype by MFC. Hematopoietic stem cells (HSCs) gating was based on CD45dim/SSC and CD34+CD38low/- expression. Leukemic stem cells (LSC) fractional change was analyzed using CD371 (CLL-1), CD366 (TIM3), and CD45RA percent of positive over HSCs. A chart review was conducted to determine correlation between LSC fractional change and clinical outcome. Statistical analysis was performed using GraphPad Prism version 9. Results: Fifty AML cases with both pre- and post-treatment data from a single institution in the past 3 years were included in this study. Consistent with published literature, patients with significant reduction in LSC subsets was associated with longer remission, while patients with no significant decrease in the LSC subsets demonstrated no or only a temporary remission. Intriguingly, several patients with drastic reduction in LSC after induction chemotherapy achieved complete remission, despite initial post-treatment bone marrow showing persistence of ">5% leukemia blasts” indicating possibly failed induction therapy. In contrast, in patients with persistently high or increased LSC fraction post-treatment, overt clinical relapse occurred quickly despite "absence” or <1% of leukemia blast differential counts in initial bone marrow. In a series of patients who received allogeneic stem cell transplant (Allo-SCT), rise of LSC fraction post Allo-SCT was associated with early AML relapse (within 6 months), while the decrease of LSC fraction was associated with prolonged remission (Representative patient cases shown in Figure 1). Lastly, among the three LSC-specific markers analyzed, the changes in LSC characterized by CLL-1 expression showed the best correlation with clinical course. In addition, the LSC fraction measured by CLL-1 in the peripheral blood is highly correlated with that of the bone marrow (R2=0.93, P<0.0001). Conclusion: This retrospective study explored the value and applicability of LSC detection in routine clinical practice. Importantly, conventional methods relying on evaluating leukemic blast counts in post-treatment bone marrow can sometimes over- or under- estimate the benefit of certain treatment regimen, leading to inappropriate continuation of the same treatment or switch of a potentially effective treatment regimen. In those groups of patients, the change in LSC fraction provides additional information for early treatment response evaluation, refines outcome prediction, and helps with treatment regimen selection. Trending LSC fractional change identifies impending relapse in post Allo-SCT. LSC fractional change determined by CLL-1 showed the best clinical correlation and should be incorporated into routine evaluation for AML patient in clinical practice, and possibly for those participating in investigational trials. Future studies will focus on collecting more data to validate above findings, determining the thresholds of LSC fractional change which constitute potential treatment response vs failure and testing the feasibility of tracking LSC subsets non-invasively in peripheral blood during treatment to predict therapeutic outcome and potentially guide treatment decisions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Photodynamic therapy using topical toluidine blue for the treatment of oral leukoplakia: A prospective case series.

Photodynamic therapy (PDT) is a minimally invasive method for the treatment of oral leukoplakia (OL) through the activation of a photosensitizer, after exposure to a specific wavelength light source. To investigate the effectiveness of toluidine blue as topical photosensitizer. Eleven patients participated in this study; fifteen oral leukoplakia lesions were treated, in several sessions, with 2.5 % toluidine blue and an LED source of 630 nm wavelength. Patients were evaluated at baseline (t0), at the end of treatment cycles (t1) and one year from the end of treatment (t2). All the treated sites were photographed at each visit. Images were processed with ImageJ 1.52 software in order to obtain the areas (mm2) of the treated lesions. Comparison between data at different follow-up was performed using a paired T-test. At t1, complete response was obtained in six lesions, partial response in seven lesions while only two lesions showed no response. At t2, a further improvement was observed in two patients. The analysis of the areas showed significant reduction of the lesion size from t0 to t1 (p = 0.003), and from t1 to t2 (p = 0.01). Toluidine blue appears to be a promising photosensitizer in the photodynamic therapy of oral leukoplakia.

Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study

Efficacy and Safety of Azacitidine (AZA) in Combination with the Anti-PD-L1 Durvalumab (durva) for the Front-Line Treatment of Older Patients (pts) with Acute Myeloid Leukemia (AML) Who Are Unfit for Intensive Chemotherapy (IC) and Pts with Higher-Risk Myelodysplastic Syndromes (HR-MDS): Results from a Large, International, Randomized Phase 2 Study

How satisfied are cervical dystonia patients after 3\xa0years of botulinum toxin type A treatment? Results from a prospective, long-term observational study

BackgroundPatients with cervical dystonia (CD) typically require regular injections of botulinum toxin to maintain symptomatic control. We aimed to document long-term patient satisfaction with CD symptom control in a large cohort of patients treated in routine practice.MethodsThis was a prospective, international, observational study (NCT01753349) following the course of adult CD treated with botulinum neurotoxin type A (BoNT-A) over 3 years. A comprehensive clinical assessment status was performed at each injection visit and subjects reported satisfaction in two ways: satisfaction with symptom control at peak effect and at the end of treatment cycle.ResultsSubject satisfaction remained relatively stable from the first to the last injection visit. At 3 years, 89.9% of subjects reported satisfaction with symptom control at peak effect and 55.6% reported satisfaction with symptom control at end of treatment cycle. By contrast, objective ratings of CD severity showed an overall reduction over 3 years. Mean ± SD Toronto Western Spasmodic Rating Scale (TWSTRS) Total scores (clinician assessed at end of treatment cycle) decreased from 31.59 ± 13.04 at baseline to 24.49 ± 12.43 at 3 years (mean ± SD reduction from baseline of − 6.97 ± 11.56 points). Tsui scale scores also showed gradual improvement; the percent of subjects with a tremor component score of 4 reduced from 12.4% at baseline to 8.1% at 3 years.ConclusionsDespite objective clinical improvements over 3 years, subject satisfaction with symptom control remained relatively constant, indicating that factors other than symptom control also play a role in patient satisfaction.

The casual effect of lifestyle factors on outcomes of assisted reproductive techniques: a protocol study on Iranian infertile couples

BackgroundAttention to additional factors affecting the success of assisted reproduction techniques (ARTs) is very important and with appropriate interventions in some of these factors, success rate can be as high as improve a lot. There is a lot of evidence that lifestyle factors can influence on ARTs outcomes. Current knowledge of the effect of combined effect of several lifestyle factors on the outcomes of ARTs is low and contradictory. The importance of the causality of this phenomenon is felt by the pandemic of inappropriate lifestyle as well as the dramatic increase in infertility in the world. The aim of this cohort study is to scrutinize the casual effect of a specific range of contemporary lifestyle factors on ARTs outcomes.MethodsA prospective cohort study will be conducted in Royan institute, Tehran, Iran. Each infertile couple will be monitored from the first visit to the end of treatment cycle. The data will be collected electronically and include the following: detailed interview about lifestyle and socioeconomic status, past medical history, general physical examination, assessment of menstrual and ovulatory status, assessment of tuboperitoneal, assessment of uterine, assessment of cervix, urogenital examination, semen analysis, anti-sperm antibodies, biochemical analysis, sperm-cervical mucus contact test, in vitro cervical mucus penetration test and sperm functional assays. To estimate the casual effect of lifestyle variables on clinical pregnancy and live birth, the obtained propensity score (PS) from generalized boosted models (GBM) will be matched between couple with and without live birth.DiscussionThis is the first study to prospectively obtain detailed information on causes of ARTs success. Determining the casual effect of lifestyle variables on ARTs success will be important to inform strategies most likely to increase the success rates in ARTs.

Cladribine induces long lasting oligoclonal bands disappearance in relapsing multiple sclerosis patients: 10-year observational study

BackgroundThere has been long-term interest in cladribine as a drug for the treatment of MS. The current study focused on the effect of cladribine on oligoclonal bands (OCB) expression in the CSF in relapsing-remitting MS (RRMS) patients observed over 10 years. Methods29 treatment-naive subjects with RRMS were prospectively enrolled and received induction therapy with subcutaneous parenteral cladribine (at a cumulative dose of 1.8 mg/kg; divided into 6 courses every 5 weeks given for 4–6 days, depending on patients’ body weight). Selected patients received maintenance doses in the follow-up period. ResultsIsoelectric focusing revealed that 55% of patients did not have OCB in CSF after cladribine treatment as compared to baseline testing when 100% of patients were positive for OCB. There were no significant differences in Expanded Disability Status Scale scores at baseline and at the end of treatment cycle between OCB-positive vs. OCB-negative subgroups. At the last follow-up, OCB-negative patients had lower disability compared to OCB-positive patients (p = 0.03). ConclusionCladribine-induced immune reconstitution leads to long lasting suppression of intrathecal humoral response, which might be an additional mechanism that enhances the therapeutic effect on disease progression in RRMS patients.

Alemtuzumab depletion failure can occur in multiple sclerosis.

Alemtuzumab is a lymphocyte-depleting antibody and one of the most effective treatments for relapsing multiple sclerosis. However, it also causes loss of immune-tolerance leading to secondary autoimmunity and marked anti-drug antibody responses. Although these anti-drug responses have been reported to be of no significance, we hypothesized that they will affect the depleting capacity and treatment response in some individuals. This was found following analysis of the regulatory submission of the pivotal phase III trials, which was obtained from the European Medicines Agency. At the population level there was lack of influence of 'ever-positive' alemtuzumab-specific antibody responses on lymphocyte depletion, clinical efficacy and adverse effects during the 2-year trial. This was not surprising as no one before the first infusion, and only 0·6% of people before the second-infusion, had pre-infusion, neutralizing antibodies (NAbs). However, at the individual level, NAbs led to poor lymphocyte depletion. Importantly, it was evident that 31% of people had NAbs and 75% had binding antibodies at the end of treatment-cycle 2, which suggests that problems may occur in people requiring additional alemtuzumab cycles. In addition, we also identified individuals, following 'post-marketing' alemtuzumab use, whose lymphocyte level was never effectively depleted after the first infusion cycle. Hence, although alemtuzumab depletes lymphocytes in most individuals, some people fail to deplete/deplete poorly, probably due to biological-response variation and NAbs, and this may lead to treatment failure. Monitoring depletion following infusion and assessment of the neutralizing response before re-infusion may help inform the decision to retreat or switch therapy to limit treatment failure.

Time to grade ≥3 adverse events in pts receiving trifluridine/tipiracil (TAS-102).

788 Background: The phase 3 RECOURSE showed that treatment with trifluridine/tipiracil in patients (pts) with refractory metastatic colorectal cancer was associated with significantly improved survival versus placebo (7.1 versus 5.3 months, respectively; HR for death 0.68, 95% CI 0.58–0.81, p &lt; 0.001), with few serious adverse events. Trifluridine/tipiracil is administered in 4-week cycles comprising 2 weeks with 5 days at 35 mg/m2 bid followed by 2 rest days, and then a 2-week rest period. Exploration of timing for AEs, particularly within the first cycle of treatment, is important for pt monitoring in the outpatient setting. Methods: We performed a post hoc analysis of the RECOURSE safety population (533 trifluridine/tipiracil; 265 placebo) to explore timing of hematological and nonhematological AEs. Results: Grade ≥ 3 adverse events (AEs) were more frequent with trifluridine/tipiracil than placebo for both hematological AEs (38% vs 0% neutropenia; 4% vs 0% febrile neutropenia; 18% vs 3% anemia; and 5% vs &lt; 1% thrombocytopenia) and nonhematological AEs (2% vs 1% nausea; 2% vs &lt; 1% vomiting; and 3% vs &lt; 1% diarrhea). The median time to nadir in cycle 1 for hematological events was 28 days (17–31) for grade ≥ 3 neutropenia, 22 days (9–39) for grade ≥ 3 anemia, and 18 days (9–33) for grade ≥ 3 thrombocytopenia; similar values were obtained in subsequent cycles. The median times to nadir and values at nadir over the whole treatment duration (all cycles) are presented in the table for hematological and nonhematological AEs. Conclusions: Hematological and nonhematological AEs with trifluridine/tipiracil appear to be most intense towards the end of treatment cycles, which is reassuring for its use in the outpatient setting. Clinical trial information: NCT01607957. [Table: see text]

Impact of hand-foot skin reaction on treatment outcome in patients receiving capecitabine plus erlotinib for advanced pancreatic cancer: A subgroup analysis from AIO-PK0104

Background. Drug-induced skin toxicity may correlate with treatment efficacy in cancer patients receiving chemotherapy or biological agents. The correlation of the capecitabine-associated hand-foot skin reaction (HFS) on outcome parameters in pancreatic cancer (PC) has not yet been investigated.Methods. Within the multicentre phase III AIO-PK0104 trial, patients with confirmed advanced PC were randomly assigned to first-line treatment with either capecitabine plus erlotinib (150 mg/day, arm A) or gemcitabine plus erlotinib (150 mg/day, arm B). A cross-over to either gemcitabine (arm A) or capecitabine (arm B) was performed after failure of the first-line regimen. Data on skin toxicity were correlated with efficacy study endpoints using uni- and multivariate analyses. To control for guarantee-time bias (GTB), we focused on subgroup analyses of patients who had completed two and three or more treatment cycles.Results. Of 281 randomised patients, skin toxicity data were available for 255 patients. Median time to capecitabine-attributed HFS was two cycles, 36 of 47 (77%) HFS events had been observed by the end of treatment cycle three. Considering HFS during first-line treatment in 101 patients treated with capecitabine for at least two cycles within the capecitabine plus erlotinib arm, time to treatment failure after first- and second-line therapy (TTF2) and overall survival (OS) both were significantly prolonged for the 44 patients (44%) with HFS compared to 57 patients without HFS (56%) (TTF2: 7.8 vs. 3.8 months, HR 0.50, p = 0.001; OS: 10.4 vs. 5.9 months, HR 0.55, p = 0.005). A subgroup analysis of 70 patients on treatment with capecitabine for at least three cycles showed similar results (TTF2: 8.3 vs. 4.4 months, HR 0.53, p = 0.010; OS: 10.4 vs. 6.7 months, HR 0.62, p = 0.056).Conclusion. The present subgroup analysis from AIO-PK0104 suggests that HFS may serve as an independent clinical predictor for treatment outcome in capecitabine-treated patients with advanced PC.

Natural Killer Cell Expression of Natural Cytotoxicity Receptors Determines Relapse Risk in Elderly Patients with Acute Myeloid Leukemia Receiving Immunotherapy with Histamine Dihydrochloride and Interleukin-2

Background: The insufficiency of natural killer (NK) cells in acute myeloid leukemia (AML) and the purported role of NK cells for prognosis have inspired the use of NK cell-based immunotherapies for relapse prevention, including the administration of NK cell-activating cytokines. A previous phase III trial using immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) was shown to significantly prevent relapse in patients who had achieved complete remission (CR) and completed the phase of consolidation chemotherapy (Brune et al., Blood108:88). Details regarding the mechanisms of relapse prevention are only partly understood.Trial design and methods: In a single-armed multicenter phase IV study (Re:Mission Trial, NCT01347996) we aimed at assessing the immunomodulatory effects of HDC/IL-2 with a focus on NK cell biology and to correlate NK cell markers with relapse risk. Eighty-four patients (age 18-79, median 61.2) with AML in first CR received post-consolidation immunotherapy with HDC/IL-2 for 18 months in ten 3-week cycles with 3 (cycle 1-6) or 6 week (cycle 7-10) intervals between cycles. NK cell counts in blood and natural cytotoxicity receptor (NCR) expression were determined by flow cytometry before and after cycles 1 and 3. The trial protocol specified separate analyses in younger (<60 years old, n=37) and elderly patients (>60 years old, n=47).Results: During cycle 1, CD56bright (CD3–/16–/56bright) and CD16+ (CD3–/16+/56+) NK cell counts increased in the blood (P=3x10-8 and P=2x10-5, respectively, paired t-test, n=47, all evaluable patients) along with an increased expression intensity of the NCRs NKp30 and NKp46 in the cytotoxic CD16+ subset (P=2x10-7 and P=6x10-8, respectively, paired t-test n=47). NK cell counts declined between the end of treatment cycle 1 and the start of cycle 3. CD56bright NK cell counts typically returned to pre-treatment levels whereas CD16+ NK cell counts remained modestly elevated at the onset of cycle 3 (P=.003, paired t-test; n=46). A renewed accumulation of CD56bright and CD16+ NK cells in the blood was observed during treatment cycle 3 (P=2x10-6 and P=.007, respectively, paired t-test, n=40). Young and elderly patients showed similar fluctuations in counts of CD56bright and CD16+ NK cell within and between treatment cycles. Also, significant induction of the expression intensity of NKp30 and NKp46 on CD16+ NK was observed in young and elderly patients.Among elderly patients, expression of NKp46 in CD16+ NK cells after the first treatment cycle was associated with favorable outcome (RFS for above-median NKp46 expression in CD16+ NK cells; P=.002, HR=4.1, CI: 1.7-10.0; logrank test). Similar results, with increased likelihood of RFS, were obtained in elderly patients with NK cells showing above-median expression of NKp30. The expression intensity of NKp30 and NKp46 did not predict relapse in younger patients.Conclusion: These results highlight the impact of NK cells and NCRs for AML prognosis and suggest that NK cell expression of NCRs may determine the efficacy of immunotherapy for remission maintenance in elderly patients. DisclosuresMartner:Study sponsor Meda Pharma GmbH & Co, Bad Homburg, Germany: Honoraria, Research Funding. Brune:Study sponsor Meda Pharma GmbH & Co, Bad Homburg, Germany: Consultancy, Honoraria. Foa:Study sponsor Meda Pharma GmbH & Co, Bad Homburg, Germany: Consultancy. Hellstrand:Study sponsor Meda Pharma GmbH & Co, Bad Homburg, Germany: Consultancy, Honoraria, related to the use of HDC/IL-2 in AML Patents & Royalties, Research Funding. Off Label Use: HDC/IL-2 is approved for use within the EU for AML patients in CR <60 years old. In the abstract we discuss the potential usefulness of the drug for patients >60 years old. Thorén:Study sponsor Meda Pharma GmbH & Co, Bad Homburg, Germany: Honoraria, Research Funding.

Breast Cancer: Assessing Response to Neoadjuvant Chemotherapy by Using US-guided Near-Infrared Tomography

To assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response. The HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons. There were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively). These findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.

Adacolumn Apheresis for Treatment of Virus C Infection in Liver Transplant Recipients

The primary strategy used to manage Virus C infection(HCV) in transplant recipients is to initiate antiviral treatment if significant (defined variably) or progressive histologic disease develops. But a preemptive antiviral strategy initiates treatment within the first few weeks post-transplantation is absent. Treatment during the early phase of infection may be more easily treated than established chronic disease, as occurs with the treatment of acute hepatitis in nontransplant patients. Although HCV is a hepatocellular pathogen, there is increasing evidence that the virus can infect and persist in other cells. In particular, granulocytes and monocytes/macrophages are known to constitute extra-hepatic sites for HCV replication and dissemination. The aim of this study was to apply Adacolumn apheresis as a possible therapeutic alternative to conventional drug therapy in the management of HCV infection. Nine patients who received liver transplantation for Virus C-related cirrhosis were eligible for the study. The patients underwent five 1-hour sessions for 5 consecutive days. First treatment was performed in the anhepatic phase of liver transplant with the intent to early reduce infected granulocytes and monocytes/macrophages. The patients were evaluated during the 5 days after inclusion with and 6-month follow-up. Early apheretic treatment in anhepatic phase and for the following 4 days after transplant determined low viral load in four LT patients, negative viral load in two patients and an increase in viremia values in one patient. At follow up the viremia load was stable in 7 patients without an increase of transaminases levels. At the end of treatment cycle almost all immune cells of six patients showed maintained CD4+/CD8+ T cells ratio. The optimal timing of treatment initiation is unknown, but an early preemptive therapy is recommended to decrease the risks for recurrence of infection. Although this study investigated the responses in a small number of patients, it was shown that Adacolumn changed the cellular immunity and promoted an early virological response.

Abstract 4622: PAM4-antigen levels in the serum of patients with pancreatic carcinoma: Early detection of disease and correlation with responses to radioimmunotherapy

Abstract Background: A serum-based enzyme immunoassay (EIA) employing MAb-PAM4 demonstrates high specificity and sensitivity for detection of advanced pancreatic carcinoma (PC). We are currently exploring use of the immunoassay as a means to detect early-stage PC, as well as detection of nascent disease progression or relapse during routine post-treatment follow-up. We now also report initial results that provide correlation of serum PAM4-antigen levels with responses to radiolabeled PAM4 therapy. Methods: The PAM4-based EIA was employed for detection and quantitation of antigen in the serum of pancreatic carcinoma patients with known stage of disease (N=68). An additional 11 patients with stage-4 disease who participated in an ongoing phase-1b clinical trial to evaluate the combination of 90Y-hPAM4 IgG, (clivatuzumab tetrexate) radioimmunotherapy with low-dose, radiosensitizing, gemcitabine (Gem) were also examined. Serum specimens from this latter group were collected at baseline prior to treatment, at the end of the 4-week treatment cycle, and again at 4 weeks post-treatment (week 8 from baseline), when a CT scan was performed to determine tumor response. Results: Overall, the sensitivity of the immunoassay for detection of PC was 81%, with a 5% false-positive rate for the healthy volunteers (N=19). When examined by stage of disease, sensitivity rates were 91%, 86% and 62% for stages 3/4 advanced disease, stage-2, and stage-1 PC, respectively. For those patients who had treatment with 90Y-hPAM4 + Gem, a decrease in antigen levels greater than 40%, observed at the end of the treatment cycle (4 weeks), with sustained decline in the antigen levels at the 8-week post-treatment evaluation, provided presumptive evidence of tumor response, either stable disease (SD, N=2) or partial response (PR, N=5) by CT RECIST criteria. None of the patients with progressive disease (N=4) had a sustainable decrease in serum levels of PAM4-antigen, whereas all of the responders did. The median decrease in serum PAM4-mucin levels at the 8-week follow-up evaluation timepoint was 54% (range: 47% - 98% decrease), with a median tumor response (only SD and PR responders) being a decrease in tumor size of 37% (range: 46% decrease to 4% increase), from a baseline median primary tumor size of 10.0 cm (range 2.6 - 12.1 cm). Conclusions: These results suggest that the PAM4-based immunoassay should be further evaluated for use in the detection of early pancreatic carcinoma, as well as to evaluate tumor response to therapy. (Supported in part by grant CA096924 from the NIH.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4622.

Updated Results of a Phase I/II Trial of Autologous Peripheral Blood Progenitor Cell Transplantation with Velcade™ Maintenance as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma

Pts (median age 59 yrs, range 38–73 yrs) with intermediate- and advanced-stage multiple myeloma were assigned to maintenance therapy with bortezomib beginning a minimum of three and a maximum of four mos after the day of autologous PBPC transplantation following a standard preparative regimen of high-dose melphalan (200 mg/m2). Eligibility for the initiation of maintenance required nl organ function, post-transplant neutrophil and plt recovery (defined as ANC ≥1000 mm−3 and untransfused plt ≥30,000 mm−3). Cohorts of 3 pts each were entered at 1 of 3 dose levels of bortezomib (1.0, 1.3, and 1.6 mg/m2) given IV q wk for 3 wks followed by a 1-wk rest period constituting 1 treatment cycle for a total of 8 cycles. To-date, 30 pts were eligible for study treatment and 24 pts received at least 1 dose of maintenance. Reasons for not proceeding to maintenance included 1 pt with an ANC < 1000 mm−3, 1 pt with a serum creatinine > 2 mg/dl, and 4 additional pts unable to travel to the center. The median t from diagnosis to transplant was 11.7 mos (range, 4.9 to 59.7 mos), and the median t from autologous transplant to the initiation of bortezomib maintenance was 3.1 mos. Protocol adherence was excellent with only 1 pt missing the final dose of treatment and 1 other pt discontinuing therapy due to personal reasons. After completion of the Phase I portion of the study, the DLT was determined to be 1.6 mg/m2 based on grade 3 diarrhea in 2 pts after 2 and 3 cycles of treatment, respectively. All subsequent pts entered were treated at the MTD of 1.3 mg/m2. Other, non-dose-limiting toxicities included fatigue (19 pts), musculoskeletal pain (17pts), neuropathy (10 pts), thrombocytopenia (9 pts), nausea (9 pts), diarrhea (7 pts), Herpes zoster reactivation (6 pts), neutropenia (6 pts), cough (3 pts), as well as upper respiratory infection, chills, fever, dyspepsia, rash and anorexia (1 pt each). Disease assessment consisted of serum and urine PEP monthly for all pts, and bone marrow aspiration quarterly for those pts with nonsecretory myeloma. Repeat bone surveys were required for pts 3, 9, 15, and 21 mos post-transplant. 2 pts required termination of the study drug, 1 at the end of treatment cycle 8 and the other during cycle 3, due to unacceptable side effects. 2 separate pts terminated the study due to disease progression, 1 during cycle 5 and the other during cycle 6, respectively. One additional pt discontinued further study treatments due to personal reasons during cycle 2. All 24 pts are eligible for response assessment. 11 pts continue to be followed every 3 mos for evidence of disease recurrence in the post-treatment period while 1 pt continues on active treatment. After a median follow-up from transplantation of 22.7 mos (range 8.7 to 39.5 mo), 10 pts have relapsed while 2 have died of recurrent myeloma. The current median relapse-free survival is 20.2 mos. This phase I/II trial demonstrates that bortezomib can be safely administered as a maintenance after conventional autologous PBPC transplantation with a MTD of 1.3mg/m2 given 3 times per month for 8 mos; treatment consolidated remission achieved by autologous transplant as will be presented. However, preliminary results with bortezomib maintenance suggest that progression free survival is not appreciably prolonged by this maintenance strategy.

Phase I/II Trial of Bortezomib Maintenance in Order To Prolong Remission-Duration Following Autologous Peripheral Blood Progenitor Cell Transplantation as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma.

Pts (median age 60 yrs, range 37 – 73 yrs) with intermediate- and advanced-stage multiple myeloma were assigned to maintenance therapy with bortezomib beginning a minimum of three and a maximum of four mos after the day of autologous PBPC transplantation following a standard preparative regimen of high-dose melphalan (200 mg/m2). Eligibility for the initiation of maintenance required nl organ function, post-transplant neutrophil and plt recovery (defined as ANC ≥ 1000 mm−3 and untransfused plt ≥30,000 mm−3). Cohorts of 3 pts each were entered at 1 of 3 dose levels of bortezomib (1.0, 1.3, and 1.6 mg/m2) given IV q wk for 3 wks followed by a 1-wk rest period constituting 1 treatment cycle for a total of 8 cycles. To-date, 29 pts were eligible for study treatment and 23 pts received at least 1 dose of maintenance. Reasons for not proceeding to maintenance included 1 pt with an ANC < 1000 mm−3, 1 pt with a serum creatinine > 2 mg/dl, and 4 additional pts unable to travel to the center. The median t from diagnosis to transplant was 11.4 mos (range, 4.9 to 59.7 mos), and the median t from autologous transplant to the initiation of bortezomib maintenance was 3.7 mos. Protocol adherence was excellent with one pt missing the final dose of treatment and one other pt discontinuing therapy due to personal reasons. After completion of the Phase I portion of the study, the DLT was determined to be 1.6 mg/m2 based on grade 3 diarrhea in 2 pts after 2 and 3 cycles of treatment, respectively. All subsequent pts entered were treated at the MTD of 1.3 mg/m2. Other, non-dose-limiting toxicities included thrombocytopenia (14 pts), neuropathy (12 pts), anemia (12 pts), fatigue (11 pts), neutropenia (8 pts), musculoskeletal pain (7pts), nausea (5 pts), Herpes zoster reactivation (4 pts), diarrhea (3 pts), edema (3 pts), cough (2 pts), as well as upper respiratory infection, chills, fever, dyspepsia, and anorexia (1 pt each). Disease assessment consisted of serum and urine PEP monthly for all pts, and bone marrow aspiration quarterly for those pts with nonsecretory myeloma. Repeat bone surveys were required for pts 3, 9, 15, and 21 mos post-transplant. 2 pts required termination of the study drug, 1 at the end of treatment cycle 8 and the other during cycle 3, due to unacceptable side effects. 2 separate pts terminated the study due to disease progression, 1 during cycle 5 and the other during cycle 6, respectively. One additional pt discontinued further study treatments due to personal reasons during cycle 2. All 23 pts are eligible for response assessment. 13 pts continue to be followed every 3 mos for evidence of disease recurrence in the post-treatment period while 4 others continue on treatment. After a median follow-up from transplantation of 17.1 mos (range 4.1 to 30.3 mo), 6 pts have relapsed while none have died of recurrent myeloma. The current median relapse-free survival is 15.8 mos. This phase I/II trial demonstrates that bortezomib can be safely administered as a maintenance after conventional autologous PBPCl transplantation with an MTD of 1.3mg/m2 given 3 times per month for 8 mos; treatment consolidated remission achieved by autologous transplant as will be presented. These preliminary results, when compared to published results of autologous transplantation for myeloma, suggest that with further follow-up, bortezomib maintenance may favorably impact t- to-recurrence.

CA 19–9 as a predictor of response and survival in patients with pancreatic cancer treated with gemcitabine and cisplatin based chemotherapy

15094 Background: Radiologic evaluation of the efficacy of chemotherapy (CT) regimens in pancreatic cancer is complicated by the retroperitoneal location and the desmoplastic nature of the tumor. The aim of this study was to evaluate the role of baseline CA 19–9 and the decrease in CA 19–9 after one cycle of CT as predictors of response, time to progression (TTP) , and overall survival (OS). Methods: We conducted 3 consecutive phase II trials evaluating gemcitabine and cisplatin based CT between 1997 and 2004. A retrospective chart review of the 111 patients yielded demographic data, best response status, TTP, OS, and CA19–9 levels. Response by CA 19–9 (R-CA19–9) was defined as a decrease of = 50% in CA 19–9 after the completion of the first cycle of chemotherapy. Results: The median age was 59 years with 60% males. Median performance status (PS) was 1. No significant difference was observed across the three trials with respect to age, sex, or PS. Baseline CA19–9 was known for 102 patients, and was dichotomized near the median as: &lt; 1,000; and = 1,000 ng/mL. Lower baseline CA19–9 levels were not associated with higher radiologic response (RR) rate (p = 0.82): 22%, and 19%, respectively. Lower baseline CA19–9 was associated with longer OS, (p = 0.0057), as shown in a recent UK study. Median OS was 9.2, and 6.1 months, respectively. Similar results were observed for TTP, with p = 0.0146, and median TTP of 6.4 and 4.2 months, respectively. The change in CA19–9 from baseline to the end of treatment cycle 1 was available for 68 patients. The patients with R-CA19- 9 had a higher RR rate (29%) than did the other patients (24%), but not significantly so (p = 0.7495). The patients with R-CA19–9 had longer OS (median 8.7 vs 7.1 months) and longer TTP (median 7.1 vs 5.4 months), but not significantly so (p &gt; 0.73 for each endpoint). Conclusions: Lower baseline CA19–9 (but not R-CA19–9 after treatment cycle 1) was positively associated with OS and TTP prognosis in our patient population. A 50% decrease in CA19–9 after the first cycle of chemotherapy was not a useful predictor of response, TTP, or OS. No significant financial relationships to disclose.

Phase I/II Trial of Bortezomib Maintenance Following Autolgous Peripheral Blood Progenitor Cell Transplantation as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma.

Patients (median age 55 yrs, range 37 – 73 yrs) with chemotherapy-responsive, intermediate- and advanced-stage multiple myeloma were assigned to maintenance therapy with bortezomib beginning a minimum of three and a maximum of four months after the day of autologous peripheral blood progenitor cell transplantation following a standard preparative regimen of high-dose melphalan (200 mg/sq.m.). Eligibility for the initiation of maintenance therapy required post-transplant neutrophil and platelet recovery (defined as minimum ANC > 1000 mm−3 and untransfused platelet count of >30,000 mm−3). Cohorts of three patients each were entered at one of three dose levels of bortezomib (1.0, 1.3, and 1.6 mg/m2) given IV once weekly for 3 weeks followed by a one-week rest period constituting one treatment cycle for a total of eight treatment cycles. To-date, 17 patients were considered eligible for study treatment and 13 patients received at least one dose of maintenance therapy. Reasons for not proceeding to maintenance included one patient with an ANC < 1000 mm−3, one patient with a serum creatinine > 2mg/dl, and four additional patients unable to travel to the treatment center. The median time from diagnosis of myeloma to transplant was 8 months (range, 4 to 19 mos), and the median time from autologous transplant to the initiation of bortezomib maintenance was 4 mos. Protocol adherence was excellent with only one patient missing the final dose of treatment. After completion of the Phase I portion of the study, the dose-limiting toxicity was determined to be 1.6 mg/m2 based on grade 3 diarrhea in two patients after 2 and 3 cycles of treatment, respectively. All subsequent patients entered were treated at the maximum tolerated dose of 1.3 mg/m2. Other, non-dose-limiting toxicities included, fatigue (11 pts), anorexia (1 pt), nausea (6 pts), dizziness (3 pts), headache (4 pts), peripheral neuropathy (6 pts), thrombocytopenia (3 pts), neutropenia (1 pt), dry cough (2 pts), upper respiratory infection (3 pts), and Herpes zoster reactivation (3 pts). Disease assessment consisted of serum and urine protein electrophereses monthly for all patients, and bone marrow aspiration quarterly for those patients with nonsecretory myeloma; repeat bone surveys were required for all patients 3, 9, 15, and 21 months post transplant. While one patient required termination of study drug at the end of treatment cycle 8 due to unacceptable side effects, no patients required termination of study drug for disease progression. Six patients currently continue to be followed every three months for evidence of disease recurrence in the post-treatment period; others continue on treatment. This phase I/II trial demonstrates that bortezomib can be safely administered as a maintenance treatment following conventional autologous peripheral blood progenitor cell transplantation with a maximum tolerated dose of 1.3 mg/m2 given three times per month for eight months; treatment consolidated the remission achieved by autologous transplant as will be presented. Further study will determine the impact of bortezomib maintenance on recurrence.

Comparative study of the effects of a progestogen-only pill containing desogestrel and an intrauterine contraceptive device in lactating women

Objective To evaluate the effects of desogestrel 75μg/day, as a progestogen-only pill compared with a copper-bearing intrauterine contraceptive device (IUCD) on lactation and to study the safety of both treatments in mothers and children. Transfer of etonogestrel to breast milk was studied in a subgroup of desogestrel users. The children were to be followed up until 2.5 years of age. Design An open, non-randomised, group-comparative study in lactating women. Setting University Hospital, Reykjavik, Iceland. Participants A total of 83 lactating women; 42 received desogestrel and 41 had an IUCD inserted for seven consecutive treatment cycles of 28 days. Methods Evaluation visits were planned at baseline and at the end of treatment cycles 1, 4 and 7. The amount of breast milk was determined by weighing the infants before and after feeding, at baseline and after treatment cycles 1 and 4. Milk samples were obtained at the same time for constituent measurements. Safety was studied by structured medical examinations and by recording adverse experiences in mothers and children. Results There were no significant differences between the desogestrel and IUCD groups in composition and quantity of breast milk nor in growth and development of the children followed up to the age of 2.5 years. In the desogestrel group a slightly higher incidence of mild adverse experiences of a hormonal nature was reported among both mothers and infants. Of the children 82% were followed until 1.5 years of age and 50% until 2.5 years. Conclusion The use of desogestrel 75μg/day did not change the amount and composition of breast milk nor did it affect growth and development of the breastfed children. It appears to be a safe and effective contraceptive method for lactating women