Is Renal Thrombotic Angiopathy a Potential Problem in the Chronic Treatment of Ovarian Cancer?

UNC Kidney Center:  thrombotic microangiopathy
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Is Renal Thrombotic Angiopathy a Potential Problem in the Chronic Treatment of Ovarian Cancer?

"Treatments for recurrent ovarian cancer result in clinical
benefit and prolongation of survival times. However, our findings suggest that platinums, PLD (in large cumulative doses), bevacizumab, and possibly gemcitabine may result in cumulative kidney damage. Awareness of these long-term complications should open the way for studies on treatment strategies designed to minimize renal complications."

Abstract

Abstract Background and Objective

Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions.

(Kidney damage was defined by pathologic abnormalities
or markers of damage, including abnormalities on blood
and urine tests and radiologic studies.)

Patients and Methods. 

Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997–2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002–2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m² for >3 months and were staged according to the National Kidney Foundation guidelines.

Results. 

Thirteen patients (23%) developed stage ≥3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy. 

Conclusions. 

CKD (chronic kidney disease) is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

• Chronic kidney disease
• Ovarian cancer
• Pegylated liposomal doxorubicin
• Renal thrombotic microangiopathy

paywalled: Science behind cisplatin-induced nephrotoxicity in humans: A clinical study

Science behind cisplatin-induced nephrotoxicity in humans: A clinical study: Publication year: 2012



Objective To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.


Conclusions The present study demonstrates that, acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances, when no corrective measures were initiated.

abstract: Uroepithelial (bladder/ureter) and kidney carcinoma in Lynch syndrome (MSH2)

Uroepithelial and kidney carcinoma in Lynch syndrome [Fam Cancer. 2012] - PubMed - NCBI
 

Fam Cancer. 2012 Apr 4

Abstract

Increased risk for urological tumors has been observed in mutation carriers with Lynch syndrome (LS). In this study, we evaluated the clinical features of uroepithelial (bladder and ureter) and kidney cancers in 974 Finnish mutation carriers. Altogether 30 patients had a total of 34 urological tumors: 12 ureter, 12 bladder, and 10 kidney cancers. Urological tumor was the only tumor in 9 (30 %) patients, and metachronous other tumor occurred in 21 (70 %). The occurrence of uroepithelial cancers was significantly higher in MSH2 mutation carriers (6 %) than in MLH1 carriers (2 %) and MSH6 mutation carriers (0 %).

The mean ages of patients at the time of diagnosis were: bladder cancer, 57 years; ureter cancer, 58 years; and kidney cancer, 64 years. Overall 5-year survival rates were 70 % in bladder cancer, 81 %  in ureter cancer, and 75 % in kidney cancer.

Cancer-specific 5-year survival rates were 70 %  in bladder cancer, 91 %  in ureter cancer, and 100 % in kidney cancer.

In conclusion, early age of onset was observed in patients with uroepithelial tumors, but not in patients with kidney cancer. The frequency of uroepithelial tumors was significantly higher in MSH2 mutation carriers than in MLH1 carriers. Further studies with larger numbers of patients, however, are needed to evaluate the potential benefit of surveillance of urological tumors in LS.

free full access: Delayed Neoplastic and Renal Complications in Women Receiving Long-term Chemotherapy for Recurrent Ovarian Cancer — J. Natl. Cancer Inst.

Mechanism of action and toxicities of purgatives used for colonoscopy preparation

Take home message: Although generally safe and effective, colonic purgatives have both acute and permanent toxicities. The safest preparations utilize PEG combined with a balanced electrolyte solution. Limitations of this preparation center on the volume required and poor taste. Alternative formulations are now available; however, those using sodium phosphate have fallen out of favor due to a risk of renal toxicity

Read More: http://informahealthcare.com/doi/abs/10.1517/17425255.2011.542411

Avastin, Cancer Drug, Can Cause Kidney Damage - ABC News + patient response/ovarian cancer (proteinuria)

"........The manifestation of proteinuria, even significant proteinuria with therapy, was seen in those pilot studies," said Dr. Bryan Becker, president of the National Kidney Foundation, who is not affiliated with the group that carried out the current study.

However, some doctors said the incidence of proteinuria with the treatment is not a cause for alarm.

"The 2 to 3 percent that have proteinuria is minor," said Dr. Otis Brawley, the American Cancer Society's chief medical and scientific officer, who likewise had no involvement with this research.

It also doesn't concern 46-year-old Julie Del Giorno, a Pennsylvania woman who took Avastin to treat her ovarian cancer as part of a clinical trial last year.

Luckily, she now has no signs of cancer left.

"I'm doing really well. Everything's been fine -- my CT scans have been normal," she said.

After reading about the side effects of Avastin and consulting with her doctor, she decided to give it a try.

"There are always risks involved, and I had trust in the doctors I was working with that it was a good option," she said"....cont'd

abstract: (Avastin) Bevacizumab Increases Risk for Severe Proteinuria in Cancer Patients

Note: one very good caution when undergoing investigational drugs

"Treatment with the chemotherapeutic agent bevacizumab, a humanized mAb that neutralizes vascular endothelial growth factor, can lead to proteinuria and renal damage. The risk factors and clinical outcomes of renal adverse events are not well understood.
We performed a systematic review and meta-analysis of published randomized, controlled trials to assess the overall risk for severe proteinuria with bevacizumab.
We analyzed data from 16 studies comprising 12,268 patients with a variety of tumors. The incidence of high-grade (grade 3 or 4) proteinuria with bevacizumab was 2.2% (95% confidence interval [CI] 1.2 to 4.3%). Compared with chemotherapy alone, bevacizumab combined with chemotherapy significantly increased the risk for high-grade proteinuria (relative risk 4.79; 95% CI 2.71 to 8.46) and nephrotic syndrome (relative risk 7.78; 95% CI 1.80 to 33.62); higher dosages of bevacizumab associated with increased risk for proteinuria.
Regarding tumor type, renal cell carcinoma associated with the highest risk (cumulative incidence 10.2%).
We did not detect a significant difference between platinum- and non–platinum-based concurrent chemotherapy with regard to risk for high-grade proteinuria (P = 0.39).
In conclusion, the addition of bevacizumab to chemotherapy significantly increases the risk for high-grade proteinuria and nephrotic syndrome."

JAMA -- Relation Between Kidney Function, Proteinuria, and Adverse Outcomes (full free access)