Cancer Treatment Today » Supportive Care

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.

For Professional version see here

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

For Professional version and other elgitimate uses of Zofran see here

Hyperbaric oxygen for osteonecrosis of the jaw

M Levin, MD — Thu, 20 Sep 2012 14:40:04 +0000

Osteonecrosis, death of bone tissues, is a well known complication that can occur in different bones. Osteonecrosis of the jaw is a known complication on of several medical interventions, such as radiation and biphosphonates. It had been initially described with the biphosphonate Fosomax but began to be seen more frequently with the intravenous biphosphonates, such as Zometa. Conservative treatment is successful in approximately 50% of patients and consists of local rinses, antibiotics, and cessation of biphosphonates. Unfortunately some patients evidence progressive necrosis despite therapy and almost a half fail to completely heal. For this reason there is a great deal of interest in hyperbaric oxygen, as a therapy that has shown effectiveness front nonhealing wounds of various types as well as for osteonecrosis caused by radiation. Unfortunately, for osteonecrosis after biphosphonate use, the supporting evidence remains case reports and case series A 2006 American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws failed to recommend this therapy because of the lack of evidence.

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Allogeneic transplantation in the elderly

M Levin, MD — Tue, 18 Sep 2012 20:22:32 +0000

The ability to escalate therapy and then salvage with stem cells from a donor has been a boon for patients with many types of cancer and hematologic malignancies, making possible a chance of cures in previously hopeless situations. In addition to the ability to markedly escalate the aggressiveness of chemotherapy that can be salvaged with transplanted stem cells, these outside donor cells, if properly managed, can provide an anticancer or anti- leukemia effect without provoking a full-scale debilitating graft versus host reaction. However, allogeneic transplantation remains a difficult, costly and toxic treatment. Taking into account toxicity and complications of high-dose chemotherapy and development of graft versus host disease, as well as infectious complications, unrelated donor transplantation can be deadly for the elderly. The recent (2011) controversy about heart transplantation for the 71-year-old former Vice-President of the United States Dick Cheney brought this issue (as well as the ethical quandaries of allocating scarce organs) to public attention. Elderly patients, even those without chronic medical problems have lower reserves to tolerate or surmount toxicity.

The maximum age for allogeneic transplantation has been increasing as methods of transplantation and supportive care have advanced. Most centers are now considering unrelated donor transplantation for patients at around seventy year mark. Unfortunately this remains an ongoing source of controversy because the literature is contradictory and confusing, owing primarily to the lack of phase 3 studies, which, however, would be very difficult to do. This remains a matter for discussion between patient and physician and an individualized decision between them. The age of around 75 years is now being routinely approached in major centers.

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.

For Professional version, see here

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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The Role of Physical Therapy in Musculor Dystrophies

M Levin, MD — Mon, 20 Aug 2012 18:18:25 +0000

Muscular dystrophy (MD)is a group of genetic diseases that affect muscle function. There are more than 30 genetic mutations that can cause muscular dystrophy. Based on the clinical features, including inheritance pattern, muscles affected, and muscle biopsy features, dystriophis are dvivided into: Duchenne, Becker, Myotonic dystrophy, Facioscapulohumeral, Limb-girdle, Ocullopharyngeal, Congenital and Distal.

Physical therapy, especially regular stretching, is important in helping to maintain the range of motion(ROM) for affected muscles and to prevent or delay contractures. Strengthening less affected muscles to compensate for weakness in the more affected muscles may improve the patient’s ability to engage in activities of daily living(ADL), especially in earlier stages of milder MD. Regular exercise is important in maintaining good overall health, but strenuous exercise should be avoided because it can damage muscles. Age of the patient and degree of dysfunction are not determining criteria of employing physical therapy, as long as an improvement in ROM and ADL can be expected.

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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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Androgen and Estrogen or Progesterone Topical Creams for Vaginal Dryness After Breast Cancer Treatment – pro

M Levin, MD — Wed, 20 Jun 2012 15:38:52 +0000

Breast cancer patients often suffer menopausal symptoms, which include vaginal dryness. This distressing symptom is often treated with topical estrogen or progesterone creams; however, there remains a concern about absorption of estrogen into the body and its effect on breast cancer. Many such patients are already on tavoxifen. In a group that is treated with tamoxifen, it would appear that most systemic effect would be negated by the tamoxifen’s anti-estrogen blockade but the question remains hotly debated. In regards to systemic estrogens, several observational studies and systematic reviews suggest no greater risk for breast cancer recurrence among breast cancer survivors treated with hormone replacement therapy(HRT). While systemic estrogens are nevertheless generally avoided because of an abundance of caution following estrogen receptor-positive breast cancer, vaginal estrogens are widely used to treat symptoms of atrophic vaginitis. Small retrospective studies in breast cancer patients suggest that vaginal estrogens do not adversely affect life expectancy. Similarly, vaginal estrogens were permitted in the placebo-controlled MA.17 trial of letrozole as extended adjuvant therapy following 5 years of tamoxifen without seeming to interfere with the observed efficacy of letrozone and tamoxifen.

A recent review(Hickey et al, 2008) concluded: “Ultimately, the decision to take estrogen for severe menopausal symptoms should rest with the patient who is fully informed regarding the potential adverse effects on disease prognosis. A benefit of multidisciplinary care is the ability to calculate individual patient recurrence risks and to use this information in decision making about treatment choices. In addition, if endocrine therapies are producing severe menopausal symptoms with relatively small benefits in terms of recurrence or survival, the multidisciplinary (MD) team may advise that these can reasonably be stopped or adjusted. For women with advanced breast cancer, the issues of quality of life(QOL) are paramount and Hormonal Therapy may be considered following discussion with the patient”.

Tamoxifen treatment is a complicating factor. In postmenopausal women, tamoxifen acts as a weak estrogen in the ovaries, uterus, and vaginal epithelium. On the other hand, Tajima et al reported on the anti-estrogenic effects seen in the vaginal epithelium of premenopausal women being treated with tamoxifen for infertility. Tamoxifen may block systemic effects on topical estrogenic preparations. Leyden in 2008 writes: “In some cases, local estrogen can be an alternative option, although patients must be carefully monitored, and many may not be comfortable with this approach.” Cochrane Systemic Review in 2004 said: “In women with a history of breast cancer, systemic estrogen or progesterone therapy is contraindicated because of the increased risk of breast cancer recurrence. Vaginal estrogen preparations often are used to treat symptoms of vaginal atrophy in these patients because of the low levels of systemic absorption.”

Therefore, use of estrogen preparation, albeit cautiously, is a reasonable option in this situation. Using androgens is, on the other hand, is problematic. Androgel is an androgen containing cream that can be sued vaginally. AndroGel, an androgen, is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone, such as:

•Primary Hypogonadism (Congenital or Acquired) – testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.
•Hypogonadotropic Hypogonadism (Congenital or Acquired) – idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum levels but have gonadotropins in the normal or low range. Using it for vaginal dryness is an off-label use.

Using androgens for vaginal dryness is subject to a clinical trial: Vaginal Testosterone Cream For Atrophic Vaginitis in Women Taking Aromatase Inhibitors for Breast Cancer, NCT01122342. Results are not yet available, and I was not able to find published literature to support the safety of androgen gels for breast cancer patients.

AugDyVa.pdf

Mateya Trinkaus, Sheray Chin, Wendy Wolfman, Christine Simmons and Mark Clemons Should Urogenital Atrophy in Breast Cancer Survivors Be Treated with Topical Estrogens? The Oncologist March 2008 vol. 13 no. 3 222-231

Tajima C, Takeda B, Tamaki Y. Effect of tamoxifen on cervical mucus, vaginal smear and endometrial findings. Fertil Steril. 1979;24:23–26.

Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women (review). In: The Cochrane Library—Collaboration TC, ed. 4 Wiley, 2007

Ponzone R, Biglia N, Jacomuzzi ME, et al. Vaginal oestrogen therapy after breast cancer: is it safe? Eur J Cancer (2005) 41(17):2673-2681.

Dew JE, Wren BG, Eden JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric (2003) 6(1):45-52.

M. Hickey; C. Saunders; A. Partridge; N. Santoro; H. Joffe; V. Stearns Practical Clinical Guidelines for Assessing and Managing Menopausal Symptoms After Breast Cancer
Annals of Oncology. 2008;19(10):1669-1680.

Read the Layperson version here.

Androgen and Estrogen or Progesterone Topical Creams for Vaginal Dryness After Breast Cancer Treatment

M Levin, MD — Tue, 19 Jun 2012 17:20:16 +0000

Sequellae of treatment for breast cancer can affect the quality of life for many years after treatment. Breast cancer patients often suffer menopausal symptoms, which include vaginal dryness. This distressing symptom is often treated with topical estrogen or progesterone creams; however, there remains a concern about absorption of estrogen into the body and its effect on breast cancer. Many patients are already on tamoxifen. In a group that is treated with tamoxifen, it would appear that most systemic effect would be negated by the tamoxifen’s anti-estrogen blockade but the question remains hotly debated. In regards to systemic estrogens, which are given by mouth, several observational studies and systematic reviews suggest no greater risk for breast cancer recurrence among breast cancer survivors treated with hormone replacement therapy(HRT). While systemic estrogens are nevertheless generally avoided because of an abundance of caution following estrogen receptor-positive breast cancer, vaginal estrogens in the form of creams or ointments are widely used to treat symptoms of atrophic vaginitis(dryness and pain form intercourse). Small retrospective studies in breast cancer patients suggest that vaginal estrogens do not adversely affect life expectancy. Similarly, vaginal estrogens were permitted in the placebo-controlled MA.17 trial of letrozole as extended adjuvant therapy following 5 years of tamoxifen without seeming to interfere with the observed efficacy of letrozone and tamoxifen.

Tamoxifen treatment is a complicating factor. In postmenopausal women, tamoxifen acts as a weak estrogen in the ovaries, uterus, and vaginal epithelium. On the other hand, Tajima et al reported on the anti-estrogenic effects seen in the vaginal epithelium of premenopausal women being treated with tamoxifen for infertility. Tamoxifen may block systemic effects on topical estrogenic preparations.Leydenin 2008 writes: “In some cases, local estrogen can be an alternative option, although patients must be carefully monitored, and many may not be comfortable with this approach.” Cochrane Systemic Review in 2004 said: “In women with a history of breast cancer, systemic estrogen or progesterone therapy is contraindicated because of the increased risk of breast cancer recurrence. Vaginal estrogen preparations often are used to treat symptoms of vaginal atrophy in these patients because of the low levels of systemic absorption.”

Therefore, use of estrogen preparation, albeit cautiously, is a reasonable option in this situation. You might think that if estrogens are a potential problem, vaginal androgens that suppress breast cancer growth would be safer. Still using androgens is problematic from the standpoint of evidence. AndroGel is an androgen containing cream that can be used vaginally. AndroGel, an androgen, is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone, such as:

Read the Professional version here.