A prospective multicenter (phase IIIb) trialstudy of Treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis

A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis

This open-label multicenter phase-IIIb trial was conducted at 47 German institutions; the first 25 patients analyzed in this safety analysis were recruited in 10 centers.

Background  

Treosulfan, an alkylating agent, has demonstrated activity in recurrent ovarian carcinoma. It is equieffective as oral (p.o.) and intravenous (i.v.) formulation. To explore the preference and compliance of elderly patients regarding p.o. or i.v. treosulfan for the treatment of relapsed ovarian carcinoma, women aged 65 years or older were included in this prospective multicenter study. Since elderly patients usually have several concomitant diseases and experience more treatment toxicity, an interim safety analysis was planned and performed after 25 patients finished therapy to assess the tolerability of the treatment regimens.


Table 1 - 6 

• Patient characteristics
• Concomitant diseases
• Treatment delivery
• Reasons for early therapy discontinuation [less than 12 cycles (i.v.) or 12 months of therapy 
• Non-hematological toxicities: highest grade per patient (in alphabetic order)
• Hematological toxicities: highest grade per patient

"Altogether 16 serious adverse events (SAE) were documented for nine patients. The predominant reason for SAE-reporting was hospitalization (14 reports). Death was the matter for the remaining 2 SAEs. An additional patient was hospitalized due to progressive disease and died in hospital. In all 3 cases, death was concerned as not related to study medication and progress of the underlying malignant tumor was stated as cause of death."

"In summary, the observed toxicities were in the same range as reported in previous studies with significantly younger patients and less comorbidity or with old women having received fewer previous lines of chemotherapy.

There were no unexpected hematological or non-hematological toxicities. Based on this safety analysis, treosulfan proved to be a safe and tolerable therapeutic option in elderly, heavily pretreated patients and the next step of study recruitment was initiated. Of note, the majority of patients in the interim safety population chose i.v. treosulfan over the oral application. Detailed analysis after completion of the trial will hopefully yield new insight into therapy preference and compliance of elderly patients with recurrent ovarian cancer."

Conflict of interest  The trial was supported by Medac GmbH.

Where the Oldest Die Now - NYTimes.com

Where the Oldest Die Now - NYTimes.com

".... But if people are being shuttled from home to hospital to nursing home (and possibly around again) during their last days and weeks, that’s nothing to celebrate. “Site-of-death data only tells you where you are at time of death, but nothing about the transitions leading to that point,” Dr. Teno said....."

Editorial: Clinical Trials in Elderly Ovarian Cancer Patients – Does It Make Sense? (Germany)

Editorial: Clinical trials in elderly ovarian cancer Patients - Does It Make Sense?

 "Clinical research needs clinical trials, new and generally
applicable knowledge can only be acquired if the young and
the old participate in clinical trials."

abstract: Treatment of Elderly Ovarian Cancer Patients in the Context of Controlled Clinical Trials: A Joint Analysis of the AGO Germany Experience

Treatment of Elderly Ovarian Cancer Patients in the Context of Controlled Clinical Trials: A Joint Analysis of the AGO Germany Experience

Summary
 
Background:

Age remains a negative prognostic factor in ovarian cancer (OC). 3 separate analyses by the AGO (Arbeitsgemeinschaft Gynaekologische Onkologie) give insight into the treatment of elderly patients (EPs) in the context of controlled clinical trials (CCTs).

Methods:
1 retrospective study evaluated the reasons for non-enrolment into CCTs of patients with advanced OC in AGO centers. 2 other exploratory age-specific analyses of a phase III trial in advanced OC treated with platinum/ paclitaxel evaluated (1) feasibility, toxicity and quality of life (QoL) and (2) the clinical outcome.  

Results: 
Non-study patients were significantly older (66.7 vs. 57.2 years). Reasons for non-enrolment were predominantly predefined exclusion criteria, numeric age, and the patient’s decision. The phase III trial confirmed an under-representation of EPs. Cycle delivery was significantly lower and discontinuation more frequent in EPs than in younger patients (YPs), although QoL, toxicity, cycle delays, and dose reductions were comparable. Delivery of cycles was prognostically significant in EPs but not YPs. The survival advantage of YPs remained significant even in completely debulked patients.

Conclusion:
There is some kind of investigator reservation for the treatment of EPs, which not only applies for the enrolment into clinical trials but also for the treatment, even under CCT conditions, with impact on outcome.

Elderly Frequently 'Undertriaged' in Emergency Departments

Elderly Frequently 'Undertriaged' in Emergency Departments

"Finally, the authors investigated reasons for inadequate triage. The most common reason for undertriage was neglect of high-risk situations, sometimes in combination with abnormal vital signs or in combination with severe pain or distress.
The second most important reason for undertriage was inappropriate interpretation of vital signs, sometimes in combination with severe pain or distress, high-risk situations, or an altered mental status.
"[I]nadequate triage appears to be due to a lack of adherence to the Emergency Severity Index algorithm rather than to an inherent deficit of the algorithm itself," the researchers conclude."


Ann Emerg Med. Published online March 9, 2012. Abstract
Conclusion
"In our study, older patients were at risk for undertriage. However, our results suggest that the Emergency Severity Index is reliable and valid for triage of older patients."

April 2011 index: Journal of Geriatric Oncology - Current Issue

example (abstract):

Volume 2, Issue 2, Pages 99-104 (April 2011)
Clinical aspects of the management of elderly women diagnosed with gynecologic malignancies: Treatment decisions and choices
The number of elderly women diagnosed with gynecologic cancer is increasing. This paper reviews the current trends in the management of elderly gynecologic cancer patients. Our goal is to identify critical issues that must be weighed when selecting treatment for elderly gynecologic oncology patients. As individuals continue to achieve longer lifespans, and the population of elderly women continues to grow, gynecologic oncologists will face new challenges regarding treatment. Due to minimal inclusion in randomized controlled trials and the influence of selection bias in many of the current studies, little evidence-based data is available regarding the most effective treatment options for this population. It is therefore unclear whether treatment should differ from that offered to younger populations, and if so under what circumstances. As of yet, there are no validated measures by which to determine tolerability and success of aggressive therapies for this population. Ultimately, each patient must be evaluated individually with regards to risk factors and prognosis, and therapy should not be withheld from elderly individuals solely on the basis of age alone.

abstract: Ovarian cancer in the elderly: Impact of surgery on morbidity and survival (France)

Note: in this study 'elderly' =  70+ yrs

CONCLUSION:

Elderly ovarian cancer patients undergo less extensive surgery and have lower OS (overall survival) despite similar postoperative morbidity, optimal resection and DFS. OS decrease could be explained by difference in the management of recurrences.

Cancer Clinical Trial: Existential Issues in Elderly People With Cancer [Conditions: Cancer] (aged people with cancer)

Detailed Clinical Trial Description

Existential and spiritual issues in elderly people with cancer are scarcely investigated with respect to the content and importance of these aspects to this patient group in terms of living with their disease and benefit from specialist health treatment and care. The present study is an independent doctoral study that also has an initial function for an intended multidisciplinary research project with the working title "Aged people with cancer".

Arms, Groups and Cohorts in this Clinical Trial

: Cancer in elderly people

abstract: Clinical aspects of the management of elderly women diagnosed with gynecologic malignancies: Treatment decisions and choices

The effect of age on the tolerability of intraperitoneal chemotherapy, complication rate, and survival in patients with ovarian cancer

Conclusions

Although elderly patients appear to tolerate fewer cycles of IP chemotherapy, they do not have higher objective complication rates or impaired PFS compared to younger patients. Age alone should not limit access to IP chemotherapy.

How Does Older Age Influence Oncologists' Cancer Management? - The Oncologist

Reference to ovarian cancer:
10.  Eisenhauer EL, Tew WP, Levine DA et al. Response and outcomes in elderly patients with stages IIIC-IV ovarian cancer receiving platinum-taxane
chemotherapy. Gynecol Oncol 2007;106:381–387.