Here is an interesting clinical trail that caught my attention.  “COLD-FX” is an over the counter cold remedy that is readily available. You can get it from Amazon for $11.00 for 30 capsules.  Does it work?  Below is the press release from Afexa, the company that makes COLD-FX.  It seems there may be small but statistically significant benefit to taking this drug.

Afexa Announces Results of Clinical Trial With Chronic Lymphocytic Leukemia Patients

EDMONTON, ALBERTA–(Marketwire – June 2, 2011) – Afexa Life Sciences Inc. (TSX:FXA) – the maker of COLD-FX® – today announced results of a clinical trial exploring the potential application of CVT-E002™, in chronic lymphocytic leukemia (CLL). The immune system, particularly antibody responses, in CLL patients is compromised and, as in all cases of immune suppression, infection is common in this population. This is the first time CVT-E002 has been studied in a cancer clinical trial exploring the role of CVT-E002 in reducing the incidence and severity of acute respiratory infections for CLL patients.

The clinical trial was led by researchers from Wake Forest Baptist Medical Centre in Winston-Salem, N.C., a U.S. National Cancer Institute (NCI) designated Comprehensive Cancer Center. The NCI-approved multi-centre, randomized, double-blind, placebo-controlled clinical trial involved 293 CLL patients from sites affiliated with Wake Forest Baptist’s Community Clinical Oncology Program Research Base. Participants were randomized to take either 400 mg of CVT-E002 or placebo per day for a minimum of 4 months during the 2008/2009 cold and flu season. The study explored the impact of CVT-E002 on the incidence, duration and severity of acute respiratory illness, the reduction in antibiotic use and overall immunological response.

The results, awaiting final peer-review, demonstrated that patients taking CVT-E002 showed a statistically significant reduction in the incidence of moderate to severe acute respiratory infection (ARI) symptoms (relative risk reduction of 20.1%; p = 0.02), and a trend of reduced incidence of moderate to severe ARI (32% vs. 39%, 95% C.I. -18%, 4%). There was no significant difference shown for patients with mild ARI symptoms, average number of ARI days or antibiotic use.

In addition, when investigators analyzed immunological response, greater seroconversion (antibody levels) was observed against nine common upper respiratory viral pathogens with CVT-E002 versus placebo (16% vs. 7%, p = 0.04). This is thought to reflect a CVT-E002 induced increase in antibody response and may be important since CLL patients generally have impaired antibody responses and immune suppression.

OK, I am inclined to give this one a pass (unless peer review counters this press release).  If you are itching to try alternate and herbal remedies in any case, this may be a relatively safe thing to try this year during the cold and flu season.  I am impressed the company actually bothered to do a multi-center, double-blinded and placebo controlled clinical trial, with close to 300 CLL patients.  Mind you, the patients took COLD-FX for 4 months, 400 milligrams each day – that would be two of the capsules/day  of the 200mg capsules Amazon had listed.  The reduction in incidence of acute respiratory infection went from 39% to 32%.  Is that a huge difference?  you be the judge.

There was an earlier study looking at similar things in geriatric (“elderly”) patients in old folks homes.  The abstract is below. ( “COLD-FX” is the brand name of CVT-002. )

J Am Geriatr Soc. 2004 Jan;52(1):13-9.

A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults.

McElhaney JE, Gravenstein S, Cole SK, Davidson E, O’neill D, Petitjean S, Rumble B, Shan JJ.

Eastern Virginia Medical School, Norfolk, Virginia, USA. jmcelhaney@uchc.edu

OBJECTIVES: To compare a proprietary extract of American ginseng, CVT-E002, with placebo in preventing acute respiratory illness (ARI) in an institutional setting during the influenza season.

DESIGN: Two randomized, double-blind, placebo-controlled trials conducted late in the 2000 (8 week) and 2000-2001 (12 week) influenza seasons.

SETTING: Long-term care setting that included nursing home and assisted living at three sites.

PARTICIPANTS: Eighty-nine (2000) and 109 (2000-2001) enrolled subjects, average age 81 and 83.5, respectively; 74% women. Approximately 90% had received influenza vaccine in each of the 2 years.

INTERVENTION: Oral twice-daily administration of a proprietary ginseng extract, CVT-E002, 200 mg or placebo.

MEASUREMENTS: ARI was defined as two new respiratory symptoms or one with a constitutional symptom. Confirmation of viral ARI was by culture (influenza or respiratory syncytial virus (RSV)) or serology for influenza. Laboratory safety monitoring was done at 0, 4, and 8 or 12 weeks.

RESULTS: An intent-to-treat analysis of pooled data corrected for drug exposure time showed that the incidence of laboratory-confirmed influenza illness (LCII) was greater in placebo- (7 cases/101 subjects) than CVT-E002-treated (1/97) groups (odds ratio (OR)=7.73, P=.033). Combined data for LCII and RSV illness were also greater in placebo- (9/101) than CVT-E002-treated (1/97) groups (OR=10.50, P=.009), for an overall 89% relative risk reduction of ARI in the CVT-E002 group.

CONCLUSION: CVT-E002 was shown to be safe, well tolerated, and potentially effective for preventing ARI due to influenza and RSV.

PMID: 14687309

As far as I can tell, CVT-E002 is a proprietary concoction of ginseng.  But apparently it works better than garden variety ginseng extracts.  Go figure. I must confess I am not really familiar with this area of research or the quality of the journals where it is published.  But there seems to be relatively little toxicity, so it might be OK to try it – if you are so inclined in any case.  But I would still pay attention to the well known benefits of social distancing and herd immunity, if I were you.

Int Immunopharmacol. 2008 Aug;8(8):1134-42. Epub 2008 May 7.

Effect of CVT-E002 (COLD-fX) versus a ginsenoside extract on systemic and gut-associated immune function.

Biondo PD, Goruk S, Ruth MR, O’Connell E, Field CJ.

Alberta Institute for Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada T6G 2P5.

CVT-E002 (sold commercially as COLD-fX) is a patented, polysaccharide-rich extract of North American ginseng (Panax quinquefolium) with purported beneficial effects on influenza and the common cold, although its mechanism of action is largely unknown. This study was conducted to determine the effects of feeding CVT-E002 versus a ginsenoside-containing extract on systemic and gut-associated immune function. For 7 days, male weanling Sprague-Dawley rats (n=10/group) were fed one of four diets: control, low CVT-E002 (450 mg/kg), high CVT-E002 (900 mg/kg), or ginsenoside (450 mg/kg). Lymphocytes were isolated from spleen, mesenteric lymph nodes and Peyer’s patches, and immune cell proportions and cytokine production were measured. IgA-positive cells in the jejunum were also assayed. CVT-E002 consumption (particularly at the higher dose) decreased spleen IL-2 and IFN-gamma production following ConA and/or LPS stimulation for 24 or 48 h (P<0.05). Also, CVT-E002-fed rats had a lower proportion of total CD3+ cells and activated T cells (P<0.05). After 48 h of ConA stimulation, spleen IL-1beta production was higher (P<0.05) for animals fed the high dose CVT-E002, whereas TNF-alpha production did not differ significantly from the control group. Feeding the ginsenoside diet resulted in lower (P<0.05) spleen IL-2 production, but the IFN-gamma, TNF-alpha and IL-1beta response to ConA was not different from control animals at 48 h. A higher proportion of jejunal IgA-positive cells was found in rats fed the ginsenoside diet (P<0.05). In conclusion, feeding CVT-E002 modifies systemic immune responses and appears to affect gut-associated immunity in a manner distinct from that of ginsenoside-containing extracts of North American ginseng.

PMID: 18550018

Disclaimer: I own no stock in Afexa, I have not been paid a dime by them.  Zero conflicts of interest.  As always, “Buyer Beware” is a good mantra to remember.

Any case, here is the link to this clinical trial.  NCT01279252 You can read all about the inclusion criteria, contact information etc by clicking on the link.

In an earlier article on the subject of painkillers, we discussed the potential danger of irreversible liver damage as a consequence of Tylenol overdose.  Did you know Tylenol overdose is one of the most common causes of acute liver damage requiring an emergency room visit in this country?  Every one of the over-the-counter pain pills have hefty advertisement budgets, I think that is a pretty safe guess.  Johnson & Johnson is reputed to spend as much as $250 million dollars in their advertisement efforts to promote Tylenol!

The abstract below comes from the “Hutch” and University of Washington.  They studied a very large number of patients roughly in our age bracket for their use of pain-killers and the risk of blood cancers. High use of Tylenol was seen to almost double the risk of blood cancers other than CLL/NHL.   There was no similar increase in incidence of blood cancers if the patients used other non-aspirin NSAIDS, ibuprofen etc.

OK, this study says there is no increased risk of CLL/SLL incidence.  Small comfort, our guys already have CLL/SLL, that train has already left the station.  How about secondary cancers? Myeloid cancers as secondary cancer have been documented in CLL patients, especially if they have been exposed to high dose alkylating agent therapy (cyclophosphamide, chlorambucil, drug combos such as FCR etc).  The Reuters article does a good job of describing the implications of this study in plain English.

Why take a chance?  For the odd aches and pains, I think it is safer for our guys to take something else.  Personally, ibuprofen (trade name “Advil“) and naproxen sodium (“Aleve“) work just fine for me when my knee starts hurting. How about you?  What do you reach for when you hurt just a little?

J Clin Oncol. 2011 May 9. [Epub ahead of print]

Long-Term Use of Acetaminophen, Aspirin, and Other Nonsteroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Prospective Vitamins and Lifestyle (VITAL) Study.

Walter RB, Milano F, Brasky TM, White E.

Fred Hutchinson Cancer Research Center; University of Washington, Seattle, WA.

PURPOSE Among previous studies examining the associations of over-the-counter analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) and incident hematologic malignancies, results were inconsistent for NSAIDs but suggested an increased risk with acetaminophen (paracetamol). Herein, we used a large prospective cohort study to examine these associations. PATIENTS AND METHODS In total, 64,839 men and women age 50 to 76 years were recruited from 2000 to 2002 to the Vitamins and Lifestyle (VITAL) study. Incident hematologic malignancies (n = 577) were identified through December 2008 by linkage to the Surveillance, Epidemiology and End Results cancer registry. Hazard ratios (HRs) associated with use of analgesics for total incident hematologic malignancies and cancer subcategories were estimated by Cox proportional hazards models. Models were adjusted for age, sex, race/ethnicity, education, smoking, self-rated health, arthritis, chronic musculoskeletal pain, migraines, headaches, fatigue, and family history of leukemia/lymphoma. Results After adjustment, there was an increased risk of incident hematologic malignancies associated with high use (≥ 4 days/week for ≥ 4 years) of acetaminophen (HR, 1.84; 95% CI, 1.35 to 2.50 for high use; P trend = .004). This association was seen for myeloid neoplasms (HR, 2.26; 95% CI, 1.24 to 4.12), non-Hodgkin’s lymphomas (HR, 1.81; 95% CI, 1.12 to 2.93), and plasma cell disorders (HR, 2.42; 95% CI, 1.08 to 5.41), but not chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; HR, 0.84; 95% CI, 0.31 to 2.28). By comparison, there was no association with risk of incident hematologic malignancies for increasing use of aspirin, nonaspirin NSAIDs, or ibuprofen. CONCLUSION High use of acetaminophen was associated with an almost two-fold increased risk of incident hematologic malignancies other than CLL/SLL. Neither aspirin nor nonaspirin NSAIDs are likely useful for prevention of hematologic malignancies.

PMID: 21555699

This question has come up in our prior discussions. The standard CLL FISH panel looks for four types of chromosomal abnormalities: 13q deletion, 12 Trisomy, 11q deletion and the most dangerous 17p deletion. Of the lot, 13 q deletion is considered the most favorable prognostic indicator. Does it make a difference if both alleles have 13q deletion? (Remember, you have a pair of 13 chromosomes, so it is possible to have one or both of these chromosomes with the relevant bit broken off. Please browse our recent article on Prognostic Indicators to understand this better).

Does it matter if majority of your CLL cells have 13q deletion, as opposed to just a small percentage? And here is a new wrinkle on the subject, does it matter if the bit broken off is a big piece as opposed to a teensy little piece? The abstract below suggests that the answer to both questions is YES. Higher percentage of CLL cells with 13q deletion is worse prognosis than lower percentage. Larger chunks of DNA broken off of the 13th chromosomes means more trouble than if the piece broken off is just a small little piece. Who knew.

All the same, I will keep an eye out to see if any other research group backs-up these findings or refutes them. It helps to be patient until the dust settles, sometimes the first word out is not always the correct finding.

Genes Chromosomes Cancer. 2011 May 11. doi: 10.1002/gcc.20885. [Epub ahead of print]

13q14 Deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia.

Dal Bo M, Rossi FM, Rossi D, Deambrogi C, Bertoni F, Del Giudice I, Palumbo G, Nanni M, Rinaldi A, Kwee I, Tissino E, Corradini G, Gozzetti A, Cencini E, Ladetto M, Coletta AM, Luciano F, Bulian P, Pozzato G, Laurenti L, Forconi F, Di Raimondo F, Marasca R, Del Poeta G, Gaidano G, Foà R, Guarini A, Gattei V.

Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.

Deletion at 13q14 is detected by fluorescence in situ hybridization (FISH) in about 50% of chronic lymphocytic leukemia (CLL). Although CLL with 13q deletion as the sole cytogenetic abnormality (del13q-only) usually have good prognosis, more aggressive clinical courses are documented for del13q-only CLL carrying higher percentages of 13q deleted nuclei. Moreover, deletion at 13q of different sizes have been described, whose prognostic significance is still unknown. In a multi-institutional cohort of 342 del13q-only cases and in a consecutive unselected cohort of 265 CLL, we investigated the prognostic significance of 13q deletion, using the 13q FISH probes locus-specific identifier (LSI)-D13S319 and LSI-RB1 that detect the DLEU2/MIR15A/MIR16-1 and RB1 loci, respectively. Results indicated that both percentage of deleted nuclei and presence of larger deletions involving the RB1 locus cooperated to refine the prognosis of del13q-only cases. In particular, CLL carrying <70% of 13q deleted nuclei with deletions not comprising the RB1 locus were characterized by particularly long time-to-treatment. Conversely, CLL with 13q deletion in <70% of nuclei but involving the RB1 locus, or CLL carrying 13q deletion in ≥70% of nuclei, with or without RB1 deletions, collectively experienced shorter time-to-treatment. A revised flowchart for the prognostic FISH assessment of del13q-only CLL, implying the usage of both 13q probes, is proposed. © 2011 Wiley-Liss, Inc.

PMID: 21563234