Robert B. Killeen MD

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Posts by Robert B. Killeen MD

Magic Mouthwash–The Last Snake Oil

Mucositis is a frequent problem encountered by hospice and palliative care services. Its treatment remains a major focus of holistic and medical therapy. Mucositis is found among 40-50% of patients receiving standard chemotherapy or head / neck radiation. This percentage is nearly doubled for bone marrow transplant patients. It can occur as a direct consequence of the radiation or chemotherapy or indirectly from infections compounding immunosuppression. Once the offending agent is stopped mucosal integrity gradually returns. In the meantime the inflammatory pain reduces the patient’s quality of life while also decreasing their oral intake leading to dehydration and malnutrition. Magic mouthwash, known by many names and aliases, reduces the pain, the disability of mucositis. Its basic constituents are as follows (1);

1) A topical anesthetic (eg. an antihistamine to reduce pain).

2) An antibiotic or antifungal.

3) A corticosteroid to decrease inflammation.

4) An antacid to coat and protect the mucosa.

The type and quantity of the constituents will vary according to the practitioner and their locale. Some common recipes are as follows (2,3);

University of Florida

60 ml Benadryl (liq)

60 ml Viscous Xylocaine

60 ml Nystatin

60 ml Maalox

sig 5 ml swish / spit q2 hrs prn

Mary’s Magic Potion

240 ml Benadryl 12.5 mg / 5 ml

1.5 grams Tetracycline

6 million units Nystatin

60 mg Hydrocortisone

sig 5 ml swish / spit QID

Weisman’s Philadelphia Mouthwash

160 ml Distilled water

80 mg Hydrocortisone

80 ml Maalox

sig 5 ml swish / spit QID

Koolstat

100 ml Cherry-flavored Kool-Aid mixed w/ 2000 ml distilled water (sugar- free)

100 ml Viscous Xylocaine 2%

100 ml Nystatin

sig 15 ml swish / spit or swallow QID

Mile’s Solution

20 ml Benadryl 12.5 mg / 5 ml

150 ml Viscous Lidocaine 2%

2 grams Tetracycline

20 ml Nystatin

100 mg Hydrocortisone (Solu-Cortef)

sig 15-30 ml swish / swallow q4-6 hrs

Data are scarce supporting the efficacy of the individual components (especially the steroids and the antibiotics) in the treatment of mucositis. However, for many of our patients who suffer from the debilitation of mucositis, the relief that this concoction offers has earned their faith and our respect.

Robert Killeen MD

References;

1) Moynihan T. Magic Mouthwash; Effective in Treating Chemotherapy Mouth Sores? MayoClinic.com – 10/31/09.

2) Tom WC. Magic Mouthwash. Pharmacist’s Letter / Prescriber’s Letter. 2007;23(7):230703.

3) Covinsky K. Management of Mucositis: Requesting Your Wisdom. Geriatrics and Palliative Blog – 7/8/10.

All-Oral Chemotherapy in Lymphoma

With the advent of hospice and palliative medicine more attention is given to palliative chemotherapy. New chemotherapy regimens are being designed to ‘heal’ rather than ‘cure’, to alleviate symptoms while maintaining the patient’s quality of life.

In the early 1990s the University of Florida developed an ‘all-oral’ protocol for use in refractory / recurrent Hodgkin’s disease. (1) This protocol was based on an earlier European regimen CEP but, as Prednimustine was unavailable in the United States, cytoxan and prednisone were substituted.(2) The resultant all-oral protocol, CCEP, was used with success not only in Hodgkin’s disease but also in refractory / recurrent non-Hodgkin’s lymphoma.(1,3) The protocol is as follows;

Cytoxan 100 mg PO day 1  10
CCNU 80 mg/m2 PO day 1
Etoposide 100 mg/m2 PO day 1  5
Prednisone 60 mg/m2 PO day 1  14

The chemotherapy was cycled every 28 days.

Several palliative lymphoma regimens were developed since but few were ‘all-oral’. A CCEP regimen (using Procarbazine instead of Prednisone) was used in AIDS-related non-Hodgkin’s lymphoma at 6 week intervals. (4) The response rate was 61% with a 39% complete response rate. However the treatment related mortality was high at 11% with myelosuppression being the most frequent and severe toxicity. Similarly, a study in Africa utilizing these agents on different schedules revealed an overall response rate of 78% with an overall survival time of 12.3 months. 33% of these patients with AIDS-related non-Hodgkin’s lymphoma survived 5 years.(5) Another protocol, PEPC, used Procarbazine in place of CCNU and was administered as metronomic therapy.(6,7) The overall response rate was 69% with a 36% complete response rate and a 33% partial response rate. No treatment related deaths were reported though myelosuppression was still a significant factor.

All-oral chemotherapy is useful both in the home and the outpatient setting. A cost analysis of the oral regimen reveals that the oral Etoposide is very expensive making the overall costs seems higher with CCEP when compared to a common intravenous (lymphoma) regimen like CHOP. However, unlike CHOP, CCEP requires no costs of pharmacy preparation, intravenous administration nor the OCN staff / facility necessary to administer it. CCEP also requires no intravenous (port) access and, by dose titration, tumor-effects can be maximized and quality-of-life maintained with myelosuppression and other toxicities kept to a minimum.

The CCEP (Cytoxan, CCNU, Etoposide and Prednisone) protocol shows great promise and should be considered by academic palliative services for study both in Hodgkin’s and non-Hodgkin’s lymphoma. Its efficacy in Hodgkin’s disease is noted in the literature however the results from the University of Florida, for Non-Hodgkin’s lymphoma, were never published. I am an affiliate of the Moffitt Cancer Center (University of South Florida) and have been told by a senior professor that since the agents in CCEP are so commonplace no drug company would ever supply the funding needed for university-level testing. How do you see this protocol proceeding on its own faith and merit? Is there any academic palliative program willing to put forward its own effort, independent of the pharmaceutical industry, to investigate this regimen further?

References;
1. Miller AM, Moreb J, Killeen RB: All-oral chemotherapy in refractory Hodgkin’s disease. Lancet 1991; 337:1408.

2. Santoro A, Viviani S, Valagussa P, Bonfante V, Bonadonna G: CCNU, Etoposide and Prednimustine (CEP) in refractory Hodgkin’s disease. Sem Onc 1986; 13 (suppl 1):23-26.

3. Killeen RB, Marsh RL: 1991. unpublished.

4. Remick SC, McSharry JJ, Wolf BC, Blanchard CG, Eastman AY, Wagner H, Portuese E, Wighton T, Powell D, Pearce T, Horton J, Ruckdeschel JC: Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin’s lymphoma. J Clin Oncol 1993; 11:1691-1702.

5. Mwanda WO, Orem J, Fu P, Banura C, Kakembo J, Onyango CA, Ness A, Reynolds S, Johnson JL, Subbiah V, Bako J, Wabinga H, Abdallah FR,
Myerson HJ, Whalen CC, Lederman MV, Black J, Ayers LW, Katongole-
Mbidde E, Remick SC: Dose-modified oral chemotherapy in the treatment
of AIDS-related non-Hodgkin’s lymphoma in East Africa. J Clin Oncol 2009;
27(21):3480-3488.

6. Coleman M, Ruan J, Furman RR, Niesvizky R, Martin P, Leonard JP: Oral combination chemotherapy for refractory / relapsed lymphoma with the PEP-C (C3) regimen (daily prednisone, etoposide, procarbazine, cyclophosphamide): low dose continuous metronomic multidrug therapy. Proc Am Soc Clin Onc 2007; 25: 457s (abst 8064).

7. Coleman M, Martin P, Ruan J, Furmann R, Niesvizky R, Elstrom R, George P,
Kaufman TP, Leonard JP: Prednisone, etoposide, procarbazine and
cyclophosphamide (PEP-C) oral chemotherapy regimen for recurring / refractory
lymphoma: Low-dose metronomic multidrug therapy. Cancer 2007; 112(10):2228-2232.