July | 2015 | Therapeutics Research Institute

Background

It is well recognized that there is wide inter-patient variability in therapeutic response to approved drugs, and that at the two extremes there might be no meaningful response or an exceptionally robust response. The question of a potential cure, however, kind of the ultimate positive response, rarely comes up, except perhaps in the context of aspirational goals by different research or disease organizations, such as “finding a cure” for chronic diseases like Cancer, Diabetes, Alzheimer’s Disease, Multiple Sclerosis, and Parkinson’s Disease. Even in such cases, it is typically not specifically articulated what is being meant by a cure or what kind of an outcome is being sought, e.g., halting or reversing disease progression, not requiring further drug treatment, all patients benefiting equally, or disease eradication. This raises some intriguing questions about what is typically thought to constitute a cure, what examples there are of diseases with cures, and what might be common characteristics of “curable” diseases. The purpose of this commentary is to explore this topic a little further, including definitions, therapeutic areas or categories where there are diseases with cures, and suggestions for future consideration.

Dictionary Definitions

The word cure comes from the Latin curare meaning, “take care of”, and cura meaning, “cure”, with the original meaning, “care, concern, or attention”. Later, the meaning became narrower, focusing on “medical care” and “successful medical treatment”, as exemplified by “curative therapy”, one of the classic types of therapies, the others being preventative (prophylactic), suppressive, replacement, supportive, and symptomatic (palliative) therapies.

The Merriam-Webster online medical dictionary¹ defines cure as “1: recovery from a disease <his cure was complete>; also: remission of signs or symptoms of a disease especially during a prolonged period of observation <a clinical cure> <5-year cure of cancer>; 2: a drug, treatment, regimen, or other agency that cures a disease <quinine is a cure for malaria>; 3: a course or period of treatment; especially, one designed to interrupt addiction or compulsive habit or to improve general health <take a cure for alcoholism> <an annual cure at a spa>.” Conventional thesaurus synonyms include relief, remedy, remission, treatment, therapeutic, and recovery.

For the task at hand, the essence of these dictionary definitions thus involves both: a) “a recovery from a disease, and its signs and symptoms” and b) “a drug, treatment, regimen, or other agency that cures a disease or condition”, thus addressing both the therapeutic response and the treatment itself, respectively.

Diseases with Cures

There appear to be three primary types of diseases with cures after therapeutic interventions, involving the following therapeutic categories: vaccinations against infectious diseases, treatments of infectious diseases, and treatments of malignancies. Note that these include both potentially serious and life-threatening acute and chronic diseases. Also note that not included is temporary relief from intermittent complaints or disorders of varying severity, such as headache, diarrhea, gastroesophageal reflux disease, seizures, or angina pectoris. Below are examples of diseases with cures, including percentages of cures, for each of these three therapeutic categories, where data is readily accessible.

Vaccinations Against Infectious Diseases – One of the great success stories in medicine has involved childhood² and adult³ vaccinations against serious and potentially deadly infectious diseases, such as measles, mumps, rubella, diphtheria, pertussis, tetanus, polio, rotavirus, hepatitis A, hepatitis B, varicella, rabies, influenza, haemophilus influenzae type b, and human papillomavirus, as well as typhoid fever, pneumococcal infection, meningococcal infection, yellow fever, and zoster. Childhood vaccinations, most of which produce immunity about 90 – 100% of the time,⁴ have had a major impact on the infections they are targeted against, including great progress towards eradicating some of the previously deadly childhood infections. The efficacy rates of other vaccines varies and is sometimes lower, e.g., the flu vaccine can typically reduce the risk of flu illness by about 50 – 60%.⁵

Treatments of Infectious Diseases – Cures have been reported for the majority of infections – bacterial, viral, or fungal – with some notable exceptions, but there is significant variability in efficacy for different infections. In contrast to vaccine immunizations and cancer treatments, there does not appear to be the same degree of consistency or ready availability of information concerning cure rates for antimicrobial treatments. Therefore, specific cure rates will not be quoted at this time. For bacterial infections, these are typically defined by anatomical locations of the infections, e.g., meningitis, pneumonia, urinary tract infection, endocarditis, osteomyelitis, sepsis and septic shock, and skin and soft tissue infection, by types of bacteria, and by drug resistance, all factors that can significantly determine the clinical outcomes. Cures of bacterial infections are well recognized in the clinical setting, and these may range from low rates to approaching 100%. For viral infections, some have highly effective treatments for suppressing viral load and infection, but without cures, e.g., HIV/AIDS, others have no effective treatment, e.g., Ebola and polio, and still others have what is thought to approach 100% cure rate, e.g., hepatitis C. For fungal infections, there are similarly variable response and cure rates, in part depending on the type of fungus and location of the infection, e.g., toenail and skin infections with higher response and cure rates, and invasive infections with lower response and cure rates.

Treatments of Malignancies – In oncology, efficacy of cancer treatments is commonly measured as survival rate, e.g., 5-year survival, 10-year survival, or 20-year survival. A complete remission of 5 years or greater is sometimes referred to as a cure, meaning that no traces are found of the cancer after treatment and that the cancer will not come back, although it is problematic to state with absolute certainty that the cancer in question will not return. With that as a general guide, three malignancies stand out as having 5-year and 10-year survival rates greater than 90%. These are testicular cancer in men, acute lymphoblastic leukemia (ALL) in children, and melanoma. For testicular cancer, survival rates vary by stage and type, and for patients with seminoma (all stages combined), the cure rate exceeds 90%, while for patients with low-stage seminoma or nonseminoma, the cure rate approaches 100%.⁶ For childhood acute lymphoblastic leukemia, 5-year survival is reported to be approximately 90% for children younger than 15 years, and about 75% for adolescents aged 15 to 19 years.⁷ For melanoma, survival rates vary by disease stage, with the 5-year and 10-year survival rates for Stage IA (Stage IB) being around 97% (92%) and 95% (86%), respectively; the most advanced stage, Stage IV, has 5-year survival of about 15-20%.⁸ Information on survival rates for other cancers is considerably to significantly lower,⁹ with pancreas cancer having the lowest survival rate, with 5-year survival ranging from 1-14%, depending on disease staging.¹⁰

Comments

Considering the medical significance of treatment cures, it is somewhat surprising how limited attention this topic gets. One possible explanation may be that cures appear to be limited to few disease types with different treatment modalities and assessment methodologies, as well as related definitions. Although the operational definitions of a cure vary among the three therapeutic categories examined, i.e., prevention of infections, treatment of infections, and treatment of malignancies, at a high level, they principally focus on “a recovery from (added: or prevention of) a disease, and its signs and symptoms”, rather than “a drug, treatment, regimen, or other agency that cures a disease or condition”.

An initial assessment of the these three therapeutic categories having diseases with cures shows that they do share the following characteristics:

The treatments do not need to be successful in all patients to be considered curative. This is most notable in cancer, where 5-year survival or 10-year survival for a given cancer can be almost anywhere on the entire spectrum from about 1 – 100%.
The treatments involve fighting/eliminating unwanted malignant cell types or microbes – cancer cells, bacteria, viruses, fungi – rather than modifying a progressive disease-related biochemical pathway or a pathophysiologic process.
The treatments in these three therapeutic categories have been known to effect cures for several decades, although individual cure rates may have improved significantly. However, no additional therapeutic categories having diseases with cures appear to have emerged in the past several decades.

Suggestions

Below are a few suggestions for future consideration:

Considering that each of the three therapeutic categories have particular aspects that may make specific reported cure rates variable, e.g., vaccinations may require booster vaccinations, treatments of infections may be affected by comorbidity, age and other factors, and cancer survival rates may not translate directly to cure rates, it is suggested that common assessment methodology be used for each of these to the extent possible.
Considering that there have been significant improvements in cure rates or survival rates within these three therapeutic categories over the past several decades, typically due to more efficacious treatments, when citing cure rates for a given disease, it is suggested the treatment and the year involved by specified, so that progress can be properly assessed.
Considering that cure is the ultimate positive therapeutic response, and that there will be additional therapeutic categories with diseases with cures in the future, it is suggested that cure rates be part of discussions of therapeutic response assessment.
Considering aspirational goals of finding cures for chronic progressive diseases, like those mentioned under Background above, it is suggested that these include further statements regarding the objectives of such treatments, for example, on the effects on the pathophysiologic process or disease progression, g., slowing, halting, or reversing.

References (All website references as accessed in June-July 2015)