abstract: Does long-term treatment with Doxil(®) predispose patients to oral cancer?

Does long-term treatment with Doxil(®) predispose patients to oral cancer?

Abstract

We present a possible adverse reaction related to long-term use of Doxil(®) in female patients. We believe that long-term use of Doxil(®) may predispose female patients to oral squamous cell carcinoma. The patients in this report were not exposed to the common risk factors related to oral cancer formation such as smoking or alcohol consumption.  

Both patients were 59-year-old females.

The first patient was diagnosed in 2001 with stage IIIC ovarian cancer. Seven years following treatment with Doxil(®), she was diagnosed with stage III squamous cell carcinoma of the right maxilla.

The second patient was diagnosed with Kaposi's sarcoma with evidence of spread to the lungs. Four years following treatment with Doxil(®) she was diagnosed with stage I squamous cell carcinoma of the left maxilla.

A literature review did not reveal any report on Doxil(®) and predisposition to oral cancer; however, we found an abstract that was presented at the last annual meeting of the American Society of Clinical Oncology (ASCO) by Cannon et al.

When we combine the data from Cannon et al. and the data presented here, a total of six female patients developed an epithelial carcinoma of the oral cavity following long-term treatment with Doxil(®).

We believe that a large-scale study should be initiated on patients that were treated with Doxil(®) for more than 3 years, since these patients might be at risk for developing secondary cancer of the oral cavity.

Endocyte jumps on plans for cancer drug candidate - Bioscience Technology (EC145 vs Doxil - re: Doxil drug shortage....)

Endocyte jumps on plans for cancer drug candidate - Bioscience Technology:

The Inquisitr

Endocyte jumps on plans for cancer drug candidate Bioscience Technology The study is designed to compare EC145 to the chemotherapy drug Doxil as a treatment for ovarian cancer. Enrollment stopped because of a shortage of Doxil, and the company said Tuesday that the Food and Drug Administration will allow it to import the ... Endocyte Prepares To Restart Clinical Trials For Experimental Cancer DrugThe Inquisitr Endocyte to seek European OK for ovarian cancer drugIndianapolis Star Endocyte to Submit EU Conditional Marketing Authorization Applications for ...MarketWatch (press release) Wall Street Journal -Indianapolis Business Journal all 21 news articles »

New source found for cancer drug Doxil, in short supply - USATODAY.com - Lipodox

"Patients with ovarian cancer and other deadly tumors will regain access to an important chemotherapy drug, Food and Drug Administration officials told USA TODAY in an exclusive interview Monday. The drug, Doxil, has been in short supply since last June. There are no generic versions of the drug, which is also used to treat multiple myeloma and AIDS-related Kaposi's sarcoma.

The agency says it will announce today that it has worked out a deal to temporarily import a replacement drug, called Lipodox, from an Indian company, says the FDA's Sandra Kweder. The FDA has previously inspected the company, Sun Pharma Global, which exports the drug to other companies....."

abstract: Health-related quality of life in recurrent platinum-sensitive ovarian cancer—results from the CALYPSO trial

Background: In the CALYPSO trial, carboplatin–pegylated liposomal doxorubicin (CD) demonstrated superior therapeutic index versus carboplatin–paclitaxel (CP) in patients with recurrent ovarian cancer. This paper reports the health-related quality of life (HRQoL) findings.

Conclusions: These patient-reported outcomes confirm the overall lower toxicity of CD versus CP. The improved disease-related outcomes achieved with CD were not at the expense of QoL.

Johnson & Johnson Profit Slumps 89% on Charges - WSJ.com (references to Doxil/drug shortages)

"Mr. Weldon said J&J learned a "painful lesson" from the ongoing supply shortage for its drug Doxil, which treats ovarian and other cancers, and will try to have better contingency plans to avoid such disruptions in the future.
J&'s sole supplier for Doxil, Ben Venue Laboratories, late last year suspended production at its Ohio plant to focus on fixing manufacturing deficiencies cited by government regulators, including contamination. Ben Venue, a unit of Boehringer Ingelheim GmbH, doesn't expect to have new Doxil supplies until late 2012............"

Patients left in lurch by cancer drug shortage - ABC Online

Patients left in lurch by cancer drug shortage ABC Online Hospitals are running short of an important drug used to treat several forms of cancer after its American manufacturer decided to temporarily halt production. Doxil, known as Caelyx in Australia, is used to treat breast, ovarian and a rare form of skin ... and more »

abstract: Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer.

Markman M.

Source

Cancer Treatment Centers of America, Eastern Regional Medical Center, Philadelphia, PA, USA.

Abstract

Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. The drug is frequently employed as a single agent in the platinum-resistant setting, and recently reported data reveal the superiority of the combination of PLD plus carboplatin, compared with the platinum drug plus paclitaxel, in delaying the time to disease progression in women with recurrent (potentially platinum-sensitive) disease. Current research efforts involving PLD in ovarian cancer are focusing on adding novel targeted drugs to this cytotoxic agent. The utility of such approaches in the platinum-resistant population, compared with the sequential administration of single agents active in this setting, remains to be determined.

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

full free access: Docetaxel Distribution Following Intraperitoneal Administration in Mice Journal of Pharmacy & Pharmaceutical Sciences (technical)

Note: in mice (research); technical

free full access: Sept 2010 Pegylated liposomal doxorubicin in the management of ovarian cancer

"This review aims at summarizing the available evidence and the new perspectives for the clinical role of PLD in the management of patients with epithelial ovarian cancer."

abstract: Monitoring long-term treatment with pegylated liposomal doxorubicin: how important is intensive cardiac follow-up?

"PLD is cardiac safe for long-term treatment of metastatic solid tumors. Its maximal cumulative dose remains undefined. "

Trabectedin (Yondelis) plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval (full access)

A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gyne

Blogger's Note: in the absence of full access to the article, this conclusion 'needs more research'


"CONCLUSIONS:: Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. It is possible that QOL is not compromised in patients with HFS because they may have increased social well being while coping with their disease."

Association of pegylated liposomal doxorubicin and ifosfamide in early recurrent ovarian cancer patients: A Multicenter Phase II Trial

Conclusion

The combination of PLD and continuous IFO is a feasible and efficient treatment in patients with relapsed ovarian cancer, especially with TFI between 6 and 12 months. This regimen may represent an alternative to platinum reintroduction and should be evaluated in a randomized trial.