Clinical Insights: December 2013
CE lesson worth 1.0 contact hour that is intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
STATEMENT OF NEED
The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.
Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
OVERALL EDUCATIONAL OBJECTIVES
Upon completion, participants should be able to:
- Describe new preventive options and treatments for cancer patients
- Identify options for individualizing the treatment for cancer patients
- Review new evidence to facilitate survivorship and supportive care for cancer patients
Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hours. CBRN credit is not accepted by the Michigan and Utah State licensing boards.
Dannemiller is approved as a provider of nurse practitioner continuing education by the American Association of Nurse Practitioners: AANP Provider Number 090419. The program was planned in accordance with AANP CE Standards and Policies and AANP Commercial Support Standards. It provides 1.0 contact hours of continuing education (which includes 0.0 hours of pharmacology).
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
CONTENT REVIEW STATEMENT
To resolve identified/potential conflicts of interest, the educational content was fully reviewed by a member of the Dannemiller Clinical Content Review Committee, Gloria Herrera, RN, MSN, FNP-BC, who has no financial relationships with commercial interests. The resulting certified activity was found to provide educational content that is current, evidence based and commercially balanced. *Note: Please list the reviewer(s) name and disclosure provided by Dannemiller (physician, RD, and/or NP)
The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Dannemiller or OncLive. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive of the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely upon the information contained within this educational activity.
OFF LABEL STATEMENT
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by FDA. The faculty have been asked to disclose this information when presented. The opinions expressed in the educational activity are those of the faculty. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Further, participants should appraise the information presented critically and are encouraged to consult appropriate resources for any product or device mentioned in this activity.
METHOD OF PARTICIPATION
- Read the articles in this section in its entirety.
- Go to www.dannemiller.com/onn-dec-2013.
- Complete and submit the CE posttest and activity evaluation.
- Print your Certificate of Credit.
This activity is provided free of charge to participants.
Analysis Finds Cancer Care Coordination Increases Patient Satisfaction
An analysis of cancer care coordination over the last 30 years shows that the process offers many benefits to oncology patients, including fewer hospitalizations and visits to emergency departments and increased patient satisfaction with care. Coordination also was found to confer benefits for clinicians themselves, in such areas as information sharing of best practices and better patient symptom management. The study was presented at the American Society of Clinical Oncology’s 2013 Quality Care Symposium held November 1-2, 2013, in San Diego, California (Abstract 103).
For the study, researchers analyzed PubMed, EMBASE, Medline, CINAHL, and the Cochrane Library; they identified 50 of 1241 abstracts published between 1980 and 2013; about half of these 50 studies were published after 2009, and eight met the added criteria for meta-analysis.
Benefits of Care Coordination
Based on their literature review, researchers identified the following most common care coordination interventions: patient navigators; home “telehealth” (eg, automated telephone surveys of patient symptoms during chemotherapy with responses reviewed by nurses); nurse case managers or care coordinators; and palliative care programs.
In 44 of the studies analyzed (83%), coordination resulted in improved cancer care (Box). The researchers concluded that although they found effective interventions taking place across the care spectrum, more consistent definitions of cancer care coordination are needed, along with higher quality and more comprehensive measures, to inform future effectiveness research.
“There needs to be more attention and resources paid to educating and engaging providers in coordinating cancer care and to empowering patients for self-management, including discussing survivorship planning with both their oncologists and their primary care providers,” said lead study author Sherri Sheinfeld Gorin, PhD, senior scientific consultant at the National Cancer Institute.
“Our study is the first to assess and quantify how much of a difference cancer care coordination can make.”
Kristin Barber, RN, MSN, APRN
Utah Cancer Specialists
Salt Lake City, UT
Here is an article that we should all have and submit to our administrators. It helps prove the utility of cancer care coordinators. Often these positions can be overlooked because of the lack of billable visits. This analysis that was presented at ASCO’s 2013 Quality Care Symposium, clearly gives evidence to support all oncology centers providing these specialists. With today’s focus in healthcare on costs, the most compelling evidence should be the fewer hospitalizations and emergency visits. From a clinical standpoint, the sharing of best practices among colleagues would be highly motivating for me. Lastly, anyone who wants to continue to provide quality oncology care needs to focus on patient satisfaction and management.
Depending on the institution and the needs, there are varying options for providing care coordination. The article mentions the most common interventions being navigators, telehealth, and nurse care managers and palliative care programs. For example, at a hospital in the radiology department, the patient navigators are more commonly utilized because they help decrease the time from diagnosis to delivery of cancer treatment or care. The nurse case managers are usually provided by the cancer centers or hospitals and their purpose is to coordinate between specialists, and help with referrals. Lastly, palliative care is now a specialty offered in almost every hospital and oncology clinic.
There is an abundance of data to support the use of these providers to help with symptom management. They have proven very effective for patient satisfaction and emotional well-being.
We are unfortunately in a time period where the cost of providing healthcare services is under great scrutiny. We must not forget that the goal is to provide quality oncologic care, and to do this we must involve cancer care coordinators.
Stem Cell Transplantation May Impair Sexual Health
Both men and women report a significant decline in sexual satisfaction after hematopoietic cell transplantation (HCT) that is sustained at 3-year follow-up, new research indicates (Blood. 2013. doi 10.1182/blood-2013-05-499806).
The data are from a prospective longitudinal study that documented trends in sexual activity, satisfaction, and function in autologous and allogeneic HCT recipients.
Results also showed a deleterious effect of chronic graft-versus-host disease (GVHD) on sexual satisfaction among women and multiple domains of sexual function in both men and women.
F. Lennie Wong, PhD, City of Hope National Medical Center in Duarte, California, and colleagues analyzed the results of surveys completed by 277 adults who underwent HCT for hematologic diseases at their institution over a recent 4-year period.
With survival continuing to improve among HCT recipients, quality of life (QOL) has become increasingly important, the investigators point out. Sexual wellbeing is an important aspect of QOL; however, there has been little information on the longitudinal course of sexual wellbeing as well as the sociodemographic and clinical factors that may alter this course over time.
What’s more, longitudinal studies thus far have included mostly non-Hispanic Caucasian patients and allogeneic HCT recipients and have also been limited by their small sample size and short time span.
Wong et al assessed patients using the Derogatis Interview for Sexual Function-Self Report and Derogatis Global Sexual Satisfaction Index before their HCT and at 6 months, and 1, 2, and 3 years afterwards.
The study found that 61% of men and 37% of women were sexually active before HCT. Individuals were deemed sexually active if they had intercourse at least once in the prior month. Prevalence rates for sexual activity decreased to 51% in men and increased to 48% in women 3 years post-HCT.
After HCT, both sexes reported a decrease in sexual satisfaction, P <.001. Sexual function was worse in women compared with men across all domains, P ≤.001.
The study found that chronic GVHD was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women
Exposure to total body irradiation (TBI) decreased sexual satisfaction and all domains of sexual function in men (P <.05) but not in women. While TBI has been reported to promote gonadal damage, no prior studies have documented an association between TBI and patient reported sexual dysfunction in men.
Wong et al point out that their study is notable in that it included an ethnically heterogeneous population of both allogeneic and autologous HCT recipients that was large and followed for a longer period of time than in earlier studies of sexual function after HCT.
They also note that their study had a “relatively low” dropout rate and used validated instruments to perform a detailed domain-specific assessment of sexual function.
At the same time, they recommend that their findings be interpreted carefully given some important study limitations. For example, they used census data to estimate missing data on patients’ education and income, which may have lessened the effects of socioeconomic status (SES). They were quick to point out, however, that aggregated census data have been reported to be a sound proxy for SES data in health outcomes research. Also, because data on pre-HCT treatment were not available, it was not possible to “tease out” their effects from effects due to transplant- related conditioning.
“These findings demonstrate the need to develop effective communications between the transplant team and HCT survivors in order to identify concerns related to sexual dysfunction and address them in specialized multidisciplinary settings,” the authors conclude.
Phyllis McKiernan, MSN, APN, OCN
Blood and Marrow Transplant Program
John Theurer Cancer CenterHackensack, NJ
Improved outcomes in bone marrow transplantation have resulted in increased survival for patients with hematologic malignancies. The impact of long-term complications after transplantation is more evident and can have a deleterious effect on quality of life for survivors.
One of the most common issues described by patients in quality-of-life studies after transplantation is sexual dysfunction, with transplant survivors reporting alterations in libido, sexual satisfaction, and sexual activity.1 The prospective longitudinal study published by Dr. Wong and colleagues examines trends in sexual functioning of patients at 3 years after transplantation, looking at the impact of many factors including chronic graft versus host disease (GVHD), the conditioning regimen, and sociodemographic factors. Results show both men and women report a decline in sexual functioning over time, and 50% report sexual inactivity.
The transplant team has a crucial role in recognizing patients who are at risk for decreased sexual functioning after transplantation. Although all transplant recipients are at risk, this study identifies potential risk factors for decline in sexual function, including older age, exposure to total body irradiation, chronic GHVD, and lower socioeconomic status.
Communication with the patient needs to specifically address sexual function across all domains to appropriately identify issues. Raising the awareness of providers, as well as providing education to increase comfort levels with discussing sexuality, are strategies to open the dialogue with patients to include sexual concerns.
Although efficacy has not been definitively proven, possible interventions include counseling and medical treatments such as hormone replacement or GHVD therapy. In addition, patients may feel greater satisfaction with their transplant experience if their concerns regarding sexual function are recognized and addressed by the transplant team.
The high prevalence of reported sexual problems after transplantation validates that additional research is needed to identify and evaluate effective strategies for prevention and treatment of sexual dysfunction for transplant survivors.
1. Thygesen KH, Schjodt I, Jarden M. The impact of hematopoietic stem cell transplantation on sexuality: a systematic review of the literature. Bone Marrow Transplant. 2012;47(5):716-724.
ALK-Positive Criteria for Determining Crizotinib Use May Fall Short
The criteria that are presently used to determine whether patients with non-small cell lung cancer (NSCLC) may be suitable for treatment with the ALK inhibitor crizotinib may overlook some patients who may benefit from the drug, researchers report. In particular, they noted that borderline and atypical ALK-negative cases need closer scrutiny. (Cancer. 2013. doi:10.1002/cncr.28311)
D. Ross Camidge, MD, PhD, University of Colorado Cancer Center in Denver, and associates tested 1426 NSCLC clinical specimens for ALK rearrangements.
Overall, 174 specimens were ALK-positive by conventional criteria, and 1252 were ALK-negative.
Screening patients with advanced NSCLC for an ALK rearrangement has been adopted as standard care based on the “dramatic and prolonged” objective responses that have been documented when these patients are treated with ALK inhibitor therapy, such as the orally bioavailable crizotinib, the investigators observed. As a result, identifying subsets of patients who are most likely to benefit from such treatment is important.
ALK gene rearrangements are the “primary oncogenic driver” in some types of lymphomas and solid tumors, the researchers said. The ALK Break Apart FISH (fluorescence in situ hybridization)Probe Kit is the only ALK diagnostic assay that is approved by the FDA.
Preliminary data suggested that a cutoff point of either ≥15% or >15% of cells demonstrating an ALK rearrangement by Break Apart FISH assay for classifying a tumor as ALK positive would yield few borderline cases, Camidge et al pointed out. The >15% cutoff point used in the early crizotinib studies and the ≥15% cutoff point used by the FDA “appeared to develop in a naturally occurring gap in the continuum of the assay.” However, the present “much larger series” indicates that “considerable proportions of ‘negative’ cases closely approach the established cutoff points,” they added.
Specifically, of the ALK specimens that were determined to be negative by standard criteria, 121 had ≥10% ALK positivity but were still less than the 15% level required in order to classify the tumor as ALK positive.
Overall, the findings showed that 8.5% of tumors fall below the established positivity threshold by ≤5%, and are thus deemed “borderline negative.”
In addition, 1%-2% also demonstrated atypical negative patterns, meaning that they did not satisfy the current Break Apart assay positivity criteria but have evidence of potential complex rearrangements within the ALK locus, such as 3’ ALK doublets or single 5’ ALK.
Camidge and associates said that additional examination of ALK in such cases by other diagnostic approaches such as immunohistochemistry may be needed.
“By capturing clinical outcomes from atypical negative and borderline negative FISH cases in which the second diagnostic suggests the true presence of an activating rearrangement, it should be possible to minimize missed therapeutic opportunities among the true inhibitor-sensitive, ALK-positive population,” the authors reported.
On November 20, 2013, the FDA granted regular approval for crizotinib capsules for the treatment of patients with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test.
This approval was based on demonstration of superior progression-free survival and overall response rate for crizotinib-treated patients compared with chemotherapy in patients with ALK-positive NSCLC with disease progression after platinum-based doublet chemotherapy.
Crizotinib was previously granted accelerated approval in August 2011.
David Leos, RN, MBA, OCN
Clinical Research Nurse Supervisor
Department of Radiation Oncology
UT MD Anderson Cancer Center
We are well into the age of what the literature cites as precision cancer or genomics-driven medicine. The findings presented in this article provide encouraging evidence to expand the current boundaries that define genomic testing guidelines for ALK mutations in NSCLC. This is an incremental, yet vital, step that we’d expect to see as new diagnostic technologies emerge or are refined.
In this case, the research suggests reconsidering the cutoff point for Break Apart FISH assay and the use of other diagnostic techniques such as immunohistochemistry (IHC) to improve detection rates of treatment targets in NSCLC. The original article cited case studies indicating that tumors designated as ALK-negative by FISH assay could actually be positive by incorporating other testing means to augment the assay’s true-positive rate.
Now that mutational status testing is widely accepted as a standard of treatment (or pretreatment as it were), this article sheds necessary light on the borderline cases—those thought, perhaps prematurely, not to have a potential for benefit from an ALK inhibitor. A more precise way of culling out those true inhibitor-sensitive patients who will derive benefit from those who will not would provide both safety and financial benefits. Those latter patients are more likely to experience mostly the side effects rather than the response from treatments that by any measure are not inexpensive.
As nurses, we must not only have awareness, but as much as possible, we need to be up-to-date with the increasing trove of cancer genomic information. For those of us whose patient population includes the diagnosis of NSCLC, this is a subject with which a subset of our patients will grapple and need our assistance in deciphering all of its complexity. It befits our educational role as nurses to have this knowledge for our patients and ourselves as professionals.
Subgroup Analyses Show Depth of Everolimus Benefit in BOLERO-2
New analyses of the BOLERO-2 trial found that everolimus and exemestane produced significantly longer progression- free survival (PFS) than placebo and exemestane in several previously unstudied patient subgroups. The data were presented at the 2013 Breast Cancer Symposium (Abstracts 142, 152).
The first analysis found that everolimus plus exemestane prolonged PFS in patients with hormone receptor—positive advanced breast cancer who received treatment as first-line therapy for advanced breast cancer.
The first analysis found that everolimus plus exemestane prolonged PFS in patients with hormone receptor—positive advanced breast cancer who received treatment as first-line therapy for advanced breast cancer.
The everolimus group had significantly longer PFS compared with the placebo group (11.50 vs 4.07 months, respectively; hazard ratio [HR] = 0.39; 95% CI, 0.25-0.62). Median PFS remained longer with everolimus versus placebo, regardless of whether chemotherapy was included with the prior adjuvant hormonal therapy.
Pending results from the recently launched BOLERO-4 trial, which will directly evaluate the efficacy of everolimus as a first-line therapy in patients with hormone receptor—positive advanced breast cancer, these results support the combination of everolimus plus exemestane in patients whose cancer recurs after adjuvant therapy or never responds to that therapy, said lead author Hope Rugo, MD, professor of Medicine and director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco.
“Many people have assumed that everolimus would do nothing for patients who did not initially respond to hormone therapy and then grow resistant to it, that hormone therapy simply wouldn’t work for that patient group,” Rugo said. “But these results strongly suggest that everolimus can help hormones work in patients who never respond to hormones as a monotherapy."
Rugo was also the lead author of the second trial, which analyzed genetic materials from a representative sample of 227 BOLERO-2 participants (157 in the everolimus arm and 70 in the placebo arm) to test how different mutations responded during the initial trial. Exon sequence and gene copy number variations were analyzed in 182 cancer-related genes by next-generation sequencing (NGS). Correlations with PFS were evaluated using univariate and multivariate Cox proportional hazard models.
The treatment benefit of everolimus over placebo was maintained in the subgroups defined by each of the nine genes with a mutation rate >10% (eg, PIK3CA, FGFR1, CCND1) or when less frequently mutated genes (eg, PTEN, AKT1) were included in their respective pathways. Patients with 0 or 1 genetic alterations in PI3K or FGFR pathways or CCND1 had a greater treatment effect from everolimus (HR = 0.27; 95% CI, 0.18- 0.41, adjusted by covariates, in 76% of the NGS population), indicating the value of these pathways for predicting sensitivity to everolimus in this setting.
“Almost half of the tumors had a mutation in PI3K and the others had less-common mutations that included cell cycle pathway markers, as well as fibroblast growth factor receptor and others,” Rugo said. “All patients, no matter what their individual mutations, benefited from the addition of everolimus, which was quite curious. It didn’t matter whether the patients had an activation in the PI3K pathway or not.”
But the news was not all good. “Patients whose tumors had mutations in multiple pathways, which was a small subset, seemed to have the worst overall outcome,” Rugo said, “and they did not benefit from the addition of everolimus.”
On the whole, Rugo thinks that the BOLERO-2 results and all of the subsequent analyses indicate that everolimus is a major step forward in the treatment of hormone receptor—positive breast cancer.
“We’ll have a better idea of just how major the advance is when we see the overall survival data from BOLERO-2, which should be out next year, but every indication we have so far is excellent,” Rugo said.
Janice Famorca Tran, RN, MS, AOCNP, CBCN, ANP-C
Breast cancer treatment has significantly progressed with the discovery of the different pathways that promote breast cancer. The subgroup analysis of the BOLERO-2 trial revealed that hormone-positive, HER2-negative women who had fewer mutated genes in PI3K, FGFR, or CCND1 received more benefit from everolimus than those who had multiple mutations. Almost half of the tumors had a mutation in the PI3K pathway.
Mutations in the PI3K pathway comprise the most common genetic alterations in breast cancer. Furthermore, this subgroup analysis revealed that individuals who had mutations in several pathways did worse, lending insight into the value of additional targeted therapies depending on an individual’s mutation type.
This study illustrates the importance of personalized medicine. The evolution of personalized medicine has allowed clinicians to treat patients on an individualized level, specifically tailored to one’s genetics. The focus of targeting specific genetic pathways driving breast cancer has revolutionized the treatment of breast cancer.
The results from this trial warrant continued research efforts with a concentration on the genomics of breast cancer in the management and treatment of this disease.
PARP Inhibitors Reemerge as Treatment for Serous Ovarian Cancer
The genomic instability inherent in serous ovarian cancer poses treatment challenges, but it also represents a target that can be exploited through the use of PARP inhibitors, according to Michael Birrer, MD, PhD, professor of Medicine, Harvard Medical School, and director of Gynecologic Medical Oncology at Massachusetts General Hospital in Boston.
“There is a plethora of data suggesting that serous ovarian cancers represent tumors of genetic chaos,” Birrer noted in his presentation at the 9th Annual International Symposium on Ovarian Cancer and Gynecologic Malignancies. “The question is: what do we do about it?”
Inhibiting PARP makes sense in ovarian tumors that arise from DNA repair abnormalities, Birrer explained, because PARP detects and works to repair these single-strand breaks in DNA. Thus, for example, in a woman who has inherited a germline BRCA mutation and develops ovarian cancer, inhibiting PARP in those cells should result in double-stranded breaks, and the cells will die through a process termed synthetic lethality.
Birrer pointed to phase I and II studies of the PARP inhibitor olaparib demonstrating antitumor activity in cancers associated with a BRCA1 or BRCA2 mutation that generated a lot of excitement about the oral agent, which also proved to be generally well tolerated by patients. Some subsequent studies of the agent, however, had mixed results, and study design was a factor, according to Birrer.
One outcome of the research was the finding that olaparib can be combined with chemotherapy, although Birrer was not sure that such a dose-intense approach makes sense. “What you’re doing is beating a cell over the head with a platinum compound. You’re coming back with PARP inhibiting the repair of the DNA.”
Currently, a number of PARP inhibitors, in addition to olaparib, are in clinical development or moving out of the laboratory into the clinic, said Birrer. Of these, he said, BMN-673 has “very good data,” indicating that it is much more potent than others in development, though whether this means the agent will be more effective or more toxic has not yet been determined.
Given the interesting data reported for the most studied agent, olaparib, and the many other PARP inhibitors now in development, Birrer discussed the implications for patients with serous ovarian cancers.
“We know it’s certainly going to work for the 8%-10% of women who have a family history and BRCA 1/2 mutations. It will probably work for the additional 8% who walk in the clinic with a sporadic cancer but also have a germline mutation. It’s probably going to work for the additional 5% or 6% of women with ovarian cancer that has some other mutation germline in the Fanconi pathway. And, it will probably work for an additional 5% to 10% of patients who have no germline mutation, but the tumor itself has a somatic abnormality in BRCA 1.
“You add those numbers up, it gets reasonably exciting,” said Birrer. He pointed to a 2011 Canadian study by Gelmon and colleagues, which found that olaparib treatment resulted in a 24% response rate in patients with ovarian cancer but who had non-BRCA mutation status, as well as a 41% response rate in participants with the germline mutation.
He also cited research indicating a possible role for PARP inhibitors in PTEN-deficient endometrial cancer, as well as data supporting the use of PARP inhibitors as radiation sensitizers.
“There are a lot of trials coming down the pike,” Birrer concluded. Two phase III olaparib trials should be open soon under the auspices of the Gynecologic Oncology Group, he said, as well as a randomized phase III trial of niraparib as maintenance in platinum-sensitive ovarian cancer patients. Other trials for rucaparib are also gearing up.
Even if patients are not mutation carriers, he advised, “and you think they might benefit from a PARP inhibitor, there should be no shortage of trials, and you should avail yourself of those.”
Soft Tissue Sarcoma
Aldoxorubicin More Effective Than Doxorubicin in STS
Aldoxorubicin (formerly INNO-206) has demonstrated response rates that culminated in a higher incidence of stable disease when compared with doxorubicin as a first-line treatment for patients with advanced soft tissue sarcomas, according to results from an ongoing phase IIb study.
In the study, patients treated with aldoxorubicin had an overall response rate of 22% compared with 0% in those treated with doxorubicin (P = .004). Additionally, 50% of those treated with doxorubicin had progressive disease compared with 32% of patients treated with aldoxorubicin.
The interim results from the study were released at the 18th Annual Connective Tissue Oncology Society (CTOS) Meeting held October 30-November 2, 2013 in New York City. (Poster 102).
Aldoxorubicin is a combination of doxorubicin and a novel single-molecule linker that quickly binds directly to endogenous circulating albumin through the EMCH linker. Protein-hungry tumors concentrate albumin, which increases the delivery of the linker molecule (with attached doxorubicin) to tumor sites. Doxorubicin is then released into the acidic environment of the tumor, leaving the neutral environment of healthy tissues unaffected. This proposed mechanism of action allows for greater doses of doxorubicin to be administered in a greater number of drug cycles while reducing toxic side effects.
In this phase IIb trial, 123 patients aged 18-80 years with metastatic, locally advanced, or unresectable soft tissue sarcomas were randomized 2:1 to receive 350 mg/m2 aldoxorubicin (260 mg/m2 doxorubicin equivalents) intravenously or 75 mg/m2 doxorubicin intravenously every 3 weeks for up to 6 cycles. The data presented at the CTOS meeting involved the 47 patients who remain active in the study (aldoxorubicin: n = 36; doxorubicin: n= 11).
The findings indicated that aldoxorubicin can be safely administered at doses exceeding three-and-a-half times the standard dosing of doxorubicin.
A higher percentage of patients treated with aldoxorubicin completed both 4 cycles and 6 cycles of treatment compared with those receiving doxorubicin. There was no significant reduction in cardiac function reported in the aldoxorubicin population.
Twenty-four serious adverse events (SAEs) were associated with aldoxorubicin versus six SAEs associated with doxorubicin. All SAEs were resolved, and treatment was not discontinued. One treatment-related death occurred in a patient treated with doxorubicin.
In a phase Ib/II trial, 76.9% (10 of13 patients) with relapsed or refractory soft tissue sarcoma saw clinical benefit with aldoxorubicin at the maximum tolerated dosage. Of the 13 evaluable patients, five achieved partial response, seven showed prolonged stable disease, and eight had tumor shrinkage. In the trial, median estimated progression-free survival was 6.4 months, which compares favorably with the historical median of approximately 3 months in this patient population.
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