Tutorial

This page is intended for folks using HemOnc.org for the first time, although frequent visitors may also learn about new features here. What follows are descriptions of the main features of the wiki.

Introduction

HemOnc.org was created in September 2011 as a freely accessible source of chemotherapy drug and regimen information. The site has grown considerably since then. For example, the number of regimens has increased by over 10,000% - from 21 to more than 2200! Here is a general FAQ, with much more detailed information below or on other dedicated pages:

FAQ

Q: Where do you source your information?
A: We look primarily to the published primary literature, including abstracts, and secondarily to sources such as review articles and guidelines. We are also in the process of forming an expert Editorial Board, which will provide additional information for the site. See Sources for more information.

Q: Why don't you have regimen "XYZ"?
A: For chemotherapy regimens, which make up the bulk of HemOnc.org content, we generally require that a regimen be published at least in abstract form before it can be included. We also prefer to only include regimens that have some demonstrated degree of efficacy, and have focused primarily on regimens published in 2005 or later. See Eligibility criteria for more information.

Q: Why don't you have drug "XYZ"?
A: For drugs, we focus first on capturing details on all FDA-approved antineoplastics. We have also tried to include drugs with promising results in clinical trials, preferably those with at least phase II results. Recently, we have also begun to include drugs that are approved in other countries but do not yet have an FDA approval, such as Belotecan (Camptobell).

Main page

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This is the landing page of HemOnc.org and is primarily a portal to get to the regimen pages, which are organized into four groups: 1) solid oncology; 2) malignant hematology; 3) transplant; and 4) classical (a.k.a., benign) hematology. Each section is further subdivided into disease-focused groups, driven primarily by the subspecialty organization of hematology/oncology. This also parallels the organization of our Editorial Board.

There are also many links that appear on the left-hand side navigation bar, which will appear on any page of the wiki.

Chemotherapy regimen pages

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These are probably the pages you are going to visit the most. Chemotherapy regimens are grouped into individual pages by cancer histology, or sometimes by biomarkers, e.g., HER2-positive breast cancer. Although the inclusion of a regimen on a page is not an endorsement of its efficacy, we generally only include regimens that are either current, recommended by well-known guideline organizations (e.g., NCCN, ASCO), or claimed to be efficacious by their author(s). See Eligibility criteria for more information. If you do not see the regimen that you are looking for on the page you think it should be on, it is either:

• Missing and needs to be added to HemOnc.org;
• Intentionally left off the page for not meeting one or more of the criteria just mentioned; or
• Present on an "obsolete" regimens page.

We are still establishing the standards by which a regimen would be considered "obsolete"; please see this page as an example of the work in progress. Proposed definitions of obsolete are:

• No longer recommended by any well-known guideline organization (e.g., NCCN, ASCO);
• More than 10 years from initial publication without any additional updates;
• No longer used in practice (difficult to prove, especially when considering international usage!).

On a particular regimen page, regimens are listed alphabetically under a treatment context; for example the melanoma page has four treatment contexts:

• Adjuvant therapy
• Local therapy
• Metastatic or unresectable disease
• Maintenance immunotherapy for metastatic or unresectable disease

On some pages, the regimens are further organized by whether or not they are described as part of a randomized trial or as a nonrandomized intervention or retrospective analysis.

Our long-term goal is to also organize regimens for advanced or metastatic disease into at least first-line and subsequent lines of therapy, with further subdivisions as driven by the clinical context. For example, the Renal cancer page has regimens divided into first-line, second-line, and third-line therapy.

Table of contents

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Almost every page of HemOnc.org has a table of contents, which allows you to jump quickly to the area of the page that you are most interested in. On various longer pages (e.g., the chemotherapy regimen pages) there are also "back to top" buttons that will bring you back to the table of contents.

Guidelines

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Most of the solid tumor pages now contain links to ASCO, ESMO, NCCN, or some specialty-specific guidelines. Hematology pages are still a work in progress, but will focus on ASH, ESMO, NCCN, and some specialty-specific guidelines. Given the sheer number of societies that might issue guidelines, we plan to generally restrict to these better-known sources.

Regimens

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When we use the term "regimen", we are broadly including any prescription with a disease modifying effect, and optionally additional prescriptions to manage the side effects of the disease-modifying agents (i.e., supportive medications). Since we are primarily focused on medical oncology and hematology, the majority of the regimens (or protocols; the words are interchangeable) have one or more antineoplastic or disease-modifying medications; we also have a few regimens that are radiotherapy-based. When describing a regimen, we try to use a consistent style for each chemotherapy regimen, so that you can find the information that you are looking for quickly and easily. Here are the components you will find:

Preferred name

Each regimen has a main description which we have designated as the preferred name. This may not be the most common name used in the published literature or clinical documentation, but this is what we try to capture. A few general notes:

• Single-agent regimens are titled "drug name" monotherapy.
• Two-agent regimens are generically titled "drug A" & "drug B"; the drugs are listed in alphabetical order unless one of the drugs is a monoclonal antibody or a steroid, which are listed last by convention.
• Some two-agent regimens which are widely known by an acronym are listed as such; e.g., AC and Rd.
• Three+ agent regimens are preferentially listed by their widely known acronym.
• Regimens with more than one sequential component are listed as "A, then B".
  • We are actively splitting these types of regimens into two separate regimens, "A" and "B".
• Regimens with alternating components are listed as "A/B", e.g., HyperCVAD/MA

Regimen alias(es)

For regimens that are known by an acronym, the first thing we do is spell out the acronym. Since these acronyms often contain outdated or brand-names, we include the generic names in parentheses as indicated.

• Example: CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

If there are alternative acronyms, these are also listed.

Example order sets

Many individual practitioners and organizations do not follow published regimens to the letter. This may be because the published regimen is under-specified, especially with respect to supportive medications, sequencing, and infusion times; or, it may be because local patterns influence treatment choices (again, this is probably most applicable to supportive medications such as antiemetics). For this reason, we have created a number of example order sets, which can be accessed directly or searched for. For example, the mFOLFOX 6 regimen on the colon cancer page has a link to the example orders for mFOLFOX 6 in colon cancer. There are many fewer example order sets than chemotherapy regimens currently, so this is another area where your contributions would be most appreciated!

Variants

For most regimens, there is only one variant. However, many regimens have a multitude of variants; e.g., BEAM, used as a preparative regimen for autologous hematopoietic stem cell transplantation, has (at least) 10 variants! In this case, we list each variant of a regimen that we have found, numerically and sometimes with a short description. Right now the order is not really meant to mean anything, although that may change in the future; sometimes we have placed variants in reverse chronologic order of publication, for instance. Generally we consider a variant to be significantly different dosing, significantly different numbers of cycles, or substitution of a similar but not identical medication (e.g., CHOP with prednisolone substituted for prednisone).

When two fairly similar regimens have been compared head-to-head, with a statistically significant difference, we usually treat these as separate regimens, rather than as variants. A classic example is dose-dense (q2wk) AC versus q3wk AC. Although never compared head-to-head (to our knowledge), the dose-dense strategy seemed to have superior OS in CALGB 9741.

Regimen variant identifiers

For each variant, we reference at least one publication, and more if multiple published protocols have used that variant. In order to frame the appropriate historical context, we try to find the earliest publication of that variant, although this is not always successful. Publications are listed by the last name of the first author "et al." unless in the extremely rare situation that there are only one or two authors. We then list the year of publication as the year that the manuscript was e-published (n.b., this is somewhat different than the standard protocol for bibliographies). If there is a clearly stated protocol acronym or code we list that in parentheses after the year.

Trial design

Next, we label the type of trial reporting the regimen with a three color code: 1) green for RCTs with at least 20 patients assigned to the regimen; 2) yellow for RCTs with fewer than 20 patients assigned to the regimen or non-randomized prospective trials with at least 20 patients; 3) red for non-randomized prospective trials with fewer than 20 patients or retrospective studies (of any size).

Comparator(s)

For RCTs, we provide a link directly to the comparator arm(s), in most cases. Some trial designs do not allow for an easy direct link, e.g., arm 1 is "A1, then A2" and arm 2 is "B". A1 can't directly be compared to B, in this instance. For such regimens, we have created a complex multipart regimens page.

Efficacy

For almost all phase III trials and most randomized phase II trials, we report the efficacy, as reported in the publication. Much more information is available here. If an interim update reports a change in efficacy, we denote this by a (*) as well as a narrative description just above the regimen details.

Toxicity

For some phase III trials, we report the toxicity, as reported in the original publication or in subsequent publications focused on HRQoL. Much more information is available here.

Entry criteria

Most regimens currently on HemOnc.org do not specify the entry (eligibility) criteria. Beginning with the randomized controlled trials, we are beginning to add the "top-line" entry criteria, generally of the format:

This regimen was intended for patients with disease X meeting conditions Y, Z.

This information is taken directly from the manuscript and is not yet in a standardized format. At this point reporting the more detailed inclusion and exclusion criteria is out of scope for the HemOnc.org project. See the Multiple myeloma page for an example of what this new information will look like.

Disease-modifying drugs

Now, to the actual regimen! We first list the disease-modifying drugs, which for most pages on HemOnc.org, are antineoplastics, alone or in combination. The high-level categories that we use for disease-modifying regimens are:

• Chemoimmunotherapy
• Chemoradiotherapy
• Chemotherapy
• Endocrine therapy
• Growth factor therapy
• Immunosuppressive therapy
• Immunotherapy
• Radiotherapy

Prescription details

Next, we list the disease-modifying drugs in the same order as the regimen acronym, or alphabetically in the absence of an acronym. Each drug is listed in a particular format:

Generic_name (Brand_name) units per unit measure route frequency on day(s) x (to y)

• Example #1: Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
• Example #2: Bendamustine 90 mg/m² IV once per day on days 1 & 2
  • Note: the brand name is omitted for two reasons: 1) this drug is well-recognized by its generic name and 2) there are two brand-name formulations with differing instructions for use.
• Example #3: Cyclophosphamide (Cytoxan) 100 mg/m² PO once per day on days 1 to 14
• Example #4: Doxorubicin (Adriamycin) 10 mg/m2/d IV continuous infusion on days 1 to 4 (total dose 40 mg/m²)

Generic_name (Brand_name) is always an active link to the drug page. When a primary reference provides details about infusion time, we include them.

• Example #5: Mitoxantrone (Novantrone) 8 mg/m² IV over 30 minutes once on day 1

When a primary reference provides details about infusion order, we also provide that information (this is even less common).

• Example #6: Mitoxantrone (Novantrone) 8 mg/m² IV over 30 minutes once on day 1, given after rituximab

Supportive medications

Immediately after the disease-modifying drugs, we provide information on supportive medications such as antihistamines, antiemetics, etc. as provided in the original reference. Some references provide specific drugs but omit doses or routes and we make note of this. Other references recommend a category of medications and we provide the link to one of our drug category pages, e.g. G-CSF. Supportive medication information is highly variable and sometimes not present in the original reference, in which case it is omitted.

Dose modifications

We occasionally include information on dose modifications, especially if they are integral to the regimen (e.g., DA-R-EPOCH), but this has not been a focus of the HemOnc.org project to date. Please consult the original reference if you suspect you are not treating a standard patient (e.g., age > 70 years old, reduced cardiac function, etc.).

Treatment duration

As with the drug information, we try to maintain a very consistent style for the length and number of cycles. Here are some common examples:

• 21-day cycle for 6 cycles
• 28-day cycle for 4 to 6 cycles
• 8 week course
• 28-day cycles
• 28-day cycles until progression, intolerance, or patient request to discontinue

Note that the first three examples are of limited duration, whereas the last two are indefinite. Generally, disease progression, intolerance due to side effects, or a patient's request to stop therapy are always reasons to discontinue therapy. However, we only explicitly list these types of stopping criteria when a reference also states them explicitly.

Multi-part regimens

If a reference reports on a multi-part regimen, we take one of two approaches (this is in flux, see below). If the regimen is clearly of limited duration and meant to be given as a "package" we include all of the information in one place. Here are two examples:

• AC, then T for the adjuvant treatment of breast cancer
• R-Hyper-CVAD alternating with R-MTX-Ara-C in the upfront treatment of mantle cell lymphoma

In other situations, there are clear separations between the phases of treatment. For example, the AIDA 2000 regimen to treat acute promyelocytic leukemia has an induction phase, a three-part consolidation phase, and a maintenance phase. These are all linked together but are kept separate on the regimen page. There are often criteria to move from one part to another part of a multiphase regimen like AIDA 2000, such as achieving a certain level of disease response. When these criteria are reported in the original publication, we include them as a note in italics.

Note: we are moving towards breaking apart all sequential regimens into "modules" linked by a Preceding treatment heading. For example, the first part of "AC, then T (Taxol)" for breast cancer has been merged with AC, and the second part with paclitaxel monotherapy.

References

Finally, we include all of the original references, in chronological order, that we have used to populate the regimen information. These are listed in PubMed style, and include links to the original article (which is often not free to access), the free PubMed Central article (if available), and the PubMed citation. Many references also include one of the following annotations:

• contains verified protocol: a contributor has reviewed the original article for accuracy of content
• contains protocol: a contributor was able to review the paper or the abstract, but it lacked critical details such as dosing, total number of cycles, etc.
• does not contain protocol: a contributor has reviewed the original article and determined that it does NOT contain the protocol
• contains protocol in supplement: a contributor has reviewed the original article and determined that the protocol is available, but not in the body of the manuscript; when possible, links to the supplement are also provided

If none of these statements are present, please be aware that the information present may not be wholly accurate or complete. Of course, the standard disclaimer always applies!

Updates and subgroup analyses

When a trial has updated results and/or a subsequent subgroup analysis, we nest the reference(s) underneath the original reference. Example:

1. Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. link to original article PubMed
   1. Update: Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. link to original article PubMed
   2. Subgroup analysis: Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. link to original article PubMed
   3. Subgroup analysis: Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. link to original article PubMed
   4. Update: Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. link to original article link to PMC article PubMed

Abstracts

We occasionally add regimens based on abstract presentations, before a manuscript has been published. In these cases we clearly label the reference with Abstract:. Additionally, once (if) a manuscript is published we replace the abstract reference with the published reference. If you are curious, we do preserve these abstract references as hidden fields; you will need editing privileges in order to view these.

Drug index

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Beyond the main page and the chemotherapy regimen pages, this is probably where you'll want to go next. This page is pretty self-explanatory but there are a few nuances you may be interested in:

Alphabetical list of drugs

Here, we list drugs alphabetically by their generic name. For all approved drugs, we also include their brand name (if there is more than one brand name we try to choose the most recognizable). Drugs that are under study are labeled in clinical trials. If a drug has been approved in the current or previous calendar year, we list the details right next to the drug, e.g. FDA Approved 7/3/2014. You will probably notice quickly that there are a fair number of red links, which means that the linked page does not yet exist. Help make it happen by contributing!

Drugs by category

Here, we list drugs under a number of different categories. A drug can, of course, be listed under many different categories. For instance, most drugs are categorized by at a minimum their mechanism of action, the diseases for which they are used, and the year that they were approved. See Individual drug pages for more details.

Interesting and helpful links

As the name says, these links are placed here because they have directly relevance to drugs, e.g. the ASCO-ONS Standards for Safe Chemotherapy Administration

Individual drug pages

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As with the chemotherapy regimens, we try to use a predictable style across all individual drug pages. They are sectioned as follows:

General information

Here, we provide a description of the mechanism of action (if known), as well as the route(s) and any other important information, such as links to REMS programs. For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information. For most antineoplastics, we provide links to the package insert provided by the manufacturer, as well as a locally-hosted backup.

Diseases for which it is used

These are the specific cancer histologies for which some degree of efficacy has been demonstrated. This is NOT the same as saying that the drug is FDA-approved or even on an approved compendium listing; we are merely stating that there is some evidence to support efficacy. These links will take you to the respective Chemotherapy regimen page.

Patient drug information

As indicated, these links are meant to be useful for patients.

History of changes in FDA indication

Here we try to include, at a minimum, the initial date of FDA approval for a cancer-related indication. When the information is available from the FDA, we also include the specific language regarding the approval; this is quite hard to locate for some of the older drugs. We also do our best to update this list with new indications.

Also known as

Here we provide synonyms, which can be only a few or sometimes hundreds, as is the case for dexamethasone. We try to include the original coded designators here, since these are often used colloquially for many years after a drug is approved (e.g. "CPT-11" is still in the vernacular). If you notice that a coded name or other synonym seems to be missing, this is an easy and impactful area for you to contribute to.

References

Self-explanatory

Categories

At the bottom of each drug page, there is a list of any number of categories that the drug has been assigned to. By clicking on one of these categories, you can easily move from a drug page to a list of similar drugs in the class, or a list of drugs approved in the same year, etc. These categories also feed into the drugs by category on the main drug index page.

Search box

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There is a search box in the upper right hand corner of every page. If you are looking for something on the site, a good way to start is by typing in some search terms and either pressing enter on your keyboard or clicking the magnifying glass. If there is a page which exactly matches what you've typed in, that will automatically show up, and you can go directly to that page by clicking on the name.

Left sidebar

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No matter what page you're on, you'll always see links on the left part of the page which will take you to some of the most useful pages on the site. Clicking the HemOnc.org logo will take you to the front page, which has links to all of our chemotherapy regimen pages.

References

This menu contains many potentially useful resources. We have carved out individual pages for some of the most frequently used, such as billing codes, antiemetic support, and performance status. Our vesicant and irritant chemotherapy page is one of our most heavily visited, and might very well be the way you found your way to the site.

Beyond these pages, we have an external links page with many, many more links. If you find your organization represented here, please consider linking us back!

Stay in touch

If you enjoy using HemOnc.org, we would really appreciate it if you could spread awareness through social media such as Facebook or Twitter. You are also welcome to join our mailing list. HemOnc.org is completely not-for-profit and does not have an operating budget; we rely on the voluntary contributions of users and word-of-mouth to spread awareness. Thank you for spreading the word!

Tools

This information is not really too useful for users of the site but is certainly relevant to contributors. So, if you've actually read all the way to the end of this tutorial, we strongly urge you to sign up and contribute. Thanks for reading!