Cancer Treatment Today » Drugs

Megace and Megace ES

M Levin, MD — Sun, 24 Feb 2013 05:19:38 +0000

Megace has long been shown to help weight gain in cancer and AIDS. More recently, Megace ES came on the market. The advantage is in the concentrated dose that Megace ES offers. It is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS).

The recommended adult initial dosage of Megace ES (megestrol acetate) oral suspension is 625 mg/day (5 mL/day or one teaspoon daily). The equivalent Megace dose it 800 mg and requires 20 ml. These drugs are are bioequivalent in a fed state.
However, in unfed patients Megace ES achieved 5 times greater peak plasma levels than Megace suspension. Additionally, the study demonstrated that a lower volume of Megace ES achieved maximum blood concentration more rapidly than the currently available oral suspension products.

However, the two products were not directly compared in regard to clinical effectiveness and it is not known if this pharmacokinetic advantages translate into any clinical advantage.

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Should Zofran be used empirically?

M Levin, MD — Mon, 11 Feb 2013 16:22:48 +0000

Ondansetron (Zofran) had been FDA approved for two decades and highly effective for nausea and vomiting. It is indicated for:
Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m2.
Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.
Prevention of postoperative nausea and/or vomiting.

Because it used to be very expensive, Zofran used to be used primarily for chemotherapy. As the cost dropped (now under a $1 a dose), it is came to be used in other situations. More an more commonly it is being used empirically in nursing homes. The drug is so effective, that some physicians consider using it as needed easier on the elderly patient than finding out the reason for nausea in these patients.

This strategy needs more data to be considered well supported. Zofran is not a completely innocuous drug. The U.S. Food and Drug Administration (FDA) recenlty informed healthcare professionals and the public that preliminary results from a recently completed clinical study suggest that a 32 mg single intravenous dose of ondansetron (Zofran, ondansetron hydrochloride, and generics) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as Torsades de Pointes. Consequenlty, GlaxoSmithKline (GSK) has announced changes to the Zofran drug label to remove the 32 mg single intravenous dose. While the 8 mg dose is presumably free of this complications, one remains uncomfortable about empiric use of Zofran in any clinical situation in which it has not been studied, and such a strategy needs to be validated with clinical trials

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Cymbalta for pain following oxaliplatin treatment

M Levin, MD — Sun, 26 Aug 2012 04:28:09 +0000

Oxaliplatin is a drug that can cause a fairly unique serve related pain, which can be difficult to manage. Two recent phase II studies suggested that Cymbalta (duloxetine) is effective for this pain. Both studies were in small number of patients and there weas a significant monority of patients who did not tolerate treatment. Overall benefit was modest. Both studies concluded that using this drug is feasible. This was followed by an abstract at 2012 ASCO meeting of a phase III trial. This was a placebo controlled crossover trial, meaning that one group got the drug and the other placebo, and if the palcebo did not work, patients could be crossed over to the active drug arm of the study . It found that there was no difference in duloxetine efficacy based on the specific chemo agent received. Severe (Grade 3) non-hematologic toxicity was reported by 11%, and 41% reported moderate (Grade 2) toxicities. The incidence of Grade 2+ fatigue, the most commonly reported side effect, was significantly higher in the duloxetine arm as compared to placebo (11% vs. 3%, p = 0.029). It concluded that duloxetine 60mg daily is an efficacious and well-tolerated intervention for the treatment of taxane or platinum-related painful CIPN.

This trial raised more questions than it answers. It does not prove that Cymbalta is uniquely beneficial for oxaliplaitn induced neuropathy and toxicity was significant. It was a comparison against placebo, not another analgesic or anti-depressant. Clearly, comparative studies are needed before it can be considered standard of care.

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Sancuso Patch

M Levin, MD — Wed, 22 Aug 2012 11:38:57 +0000

SANCUSO® (Granisetron Transdermal System) is FDA indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days duration; some studies show that it is effective for up to 7 days. An example of such a regimen would be a 5 day course of cisplatin. SANCUSO has been studied in head and neck cancers, gastrointestinal cancers, breast cancer and gynecological cancers. It also seems particularly suited for prevention of delayed nausea and vomiting that can be seen with drugs such as cisplatin, even if not given for 5 days, that distribute into fat and then come out after 72 hours, causing nausea days after administration of chemotherapy. NCCN recommends it in its Antiemesis guidelines on p. AE-2.

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Provigil for Cancer Fatigue

M Levin, MD — Wed, 20 Jun 2012 18:16:10 +0000

People with cancer can be very tired, because of the cancer itself or as a side effect of cancer chemotherapy. In addition, many cancer patients suffer from depression. Appetite is often affected by advanced cancer. Medications that stimulate attention and increase endurance are often used to control these symptoms. Provigil (modafinil) is a psychostimulant that was not designed for cancer patients and it is used mainly to treat people with narcolepsy. It has some troublesome side effects. In a clinical trial for narcolepsy, 74 of the 934 patients (8%) who received PROVIGIL dropped out compared to 3% of patients that received placebo. The most frequent reasons for stopping Provigil were headache, nausea, anxiety, dizziness, difficulty sleeping, chest pain and nervousness. NCCN publishes (National Cancer Centers Network) well accepted guidelines and it recommends psychostimulants for some cases of severe cancer related fatigue. Provigil is not an amphetamine and it is of a different class than other psychostimulants. Medical literature supports it for cancer fatigue and especially for the fatigue of brain cancer.

There were two prospective open-label studies of modafinil (Provigil). One study showed positive effects on fatigue that had persisted for an average of 2 years following breast cancer treatment. For these patients, fatigue severity and other measures of quality of life were significantly improved following 1 month of treatment with modafinil. Another recent study of 30 patients with malignant and benign brain tumors who were treated with surgery, radiotherapy, and/or chemotherapy found that modafinil was associated with significant improvements in fatigue scores. The most commonly reported adverse effects of modafinil treatment were headache, infection, nausea, nervousness, anxiety, and insomnia, all of which were generally mild. Randomized clinical trials of modafinil are under way to investigate its effect on cancer related fatigue in patients receiving chemotherapy and those who have completed chemotherapy or radiation therapy.

A phase III trial was presented at the 2008 meeting of the American Society of Clinical Oncology in Chicago, May 30-June 2. It included 642 patients with cancer-related fatigue who were undergoing chemotherapy for a variety of cancers. Patients were randomized to receive Provigil (n=320) or placebo (n=322) and were evaluated for fatigue, sleepiness, and depression at two different time points. Patients with severe baseline fatigue had significant improvement on Provigil compared with placebo (p=0.017). However, patients with mild to moderate fatigue did not show improvement. All patients in the study appeared to have less “sleepiness” than in the control group (p=0.002). Provigil had no effect on depression. The authors concluded that Provigil could be of benefit in treating severe cancer-related fatigue.

The subject was discussed at ASCO educational meeting in 2010.

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