Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer? PLD (pegylated liposomal doxorubicin)

Squamous Cell Carcinoma of the Oral Cavity in Non smokingWomen: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

Abstract
Purpose.
To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.

Patients and Methods.
In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed.

Results.
All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m(2) given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD.

Conclusion. 
Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer. 

The finding of oral SCC in patients on long-term PLD
maintenance should alert oncologists to have a high index of
suspicion with any oral complaints that arise, and suggests a
possible need for regular oral examinations in this treatment
population. How long to continue maintenance with PLD after
a CR has been achieved is an unanswered question. The possible
risks to patients receiving maintenance PLD beyond CR
must be weighed against the presumed benefits of delaying
ovarian cancer recurrence on an individual basis.

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

UNC Kidney Center:  thrombotic microangiopathy
                           ~~~~~~~~~~~~~~~~~~

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

Medpage SGO news: :Combo Promising for Resistant Ovarian Cancer - in Meeting Coverage, SGO from MedPage Today

Medical News:Combo Promising for Resistant Ovarian Cancer - in Meeting Coverage, SGO from MedPage Today

"....The between-group difference increased to 4 months in the subgroup of patients whose lesions had imaging-confirmed folate-receptor expression.
Overall survival did not differ between the groups, due in part to an unusually prolonged survival in the control arm, R. Wendel Naumann, MD, said here at the Society of Gynecologic Oncology meeting.
"This is the first clinical trial that has shown a benefit in progression-free survival over standardized therapy in a randomized trial in patients with platinum-resistant ovarian cancer, and we think it's pretty exciting," said Naumann, of Carolinas Medical Center in Charlotte, N.C.
"We know that EC20 scanning identifies patients who will benefit most from the combination of pegylated liposomal doxorubicin and vintafolide, as well as those who will not benefit. It appears that patients in whom all lesions are folate-receptor positive benefit the most from this combination."
A phase III randomized trial of PLD plus vintafolide has already begun, he added.............

Action Points

• This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that a compound which binds with high affinity to the folate receptor, which is expressed on the majority of epithelial ovarian cancers, and releases a cytotoxic component significantly increased progression-free survival in this phase two study.

abstract: Retrospective study comparing irinotecan (CPT-11) and pegylated liposomal doxorubicin in treatment of recurrent platinum-refractory/resistant epithelial ovarian cancer (Japan)

Blogger's Note: older studies have also included efficacy in clear cell ovarian tumors

 Abstract

PURPOSE:

The standard regimen for platinum-resistant/refractory recurrent epithelial ovarian cancer (EOC) remains to be determined. In this study, we retrospectively compared the effect of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in the treatment of platinum-resistant recurrent EOC.

METHODS:

Thirty patients who received salvage chemotherapy with CPT-11 or PLD were included in the study. CPT-11 (100 mg/m2) was administered intravenously on days 1, 8 and 15 every four weeks. PLD (50 mg/m2) was administered on day 1 every four weeks. Treatment was repeated, provided that no disease progression or intolerable toxicity occurred.

RESULTS:

Response rate in the CPT-11 group and PLD group showed no difference at 26.7% in both, while non-PD rate was 73.3% vs. 33.3%, respectively. Progression-free survival after CPT-11 treatment and PLD treatment was 28.4 weeks and 16.8 weeks, respectively. Hand-foot syndrome and mucositis were more common in the PLD group than in the CPT-11 group.

CONCLUSIONS:

The results indicate that CPT-11 is a promising drug for the treatment of platinum-resistant recurrent EOC.

Long-Term Doxorubicin Linked to Secondary Oral Cancers

".......Four patients who received long-term PLD for advanced-stage ovarian cancer developed malignant and/or premalignant lesions of the tongue and/or oral cavity. Dr. Cannon points out that there were only about 16 patients who received PLD for an extended period of time, "so 4 out of 16 patients is quite high."
All 4 of the patients had received maintenance therapy with PLD for at least 3 years. Of this group, 3 women were subsequently diagnosed with squamous cell carcinoma (SCC) of the tongue and/or oral cavity, and 1 patient was diagnosed with sublingual mucosa high-grade dysplasia. All 3 cases of SCCs were negative for human papillomavirus.

Of note, said Dr. Cannon, was a patient who presented with 3 separate lesions of SCC of the oral cavity.

"I don't think this is a coincidence, that 4 of 16 patients receiving this treatment developed oral cancers," he said. "If this treatment for ovarian cancer becomes more popular, then this is something that should become known. Early dental screening would need to be initiated, and the treatment may need to be stopped after a certain time period."

It is relatively uncommon for ovarian cancer patients to receive PLD for this length of time.......cont'd

also: see chart