ChemoOrders.com Methodology
How Treatment Regimens Are Selected:
Doctors, ONS-Certified nurses, pharmacists and Mid-Level Providers—both NPs and PAs—reviewed FDA approved and compendia listed therapeutics by disease and indication as supported by peer-reviewed literature. Further analysis by NCCN and ASCO guidelines, and package insert indication, was performed. The result of this analysis is the presentation of a list of treatment options per disease and/or indication qualified by a key to denote FDA approval (F), compendia listing (C), and any patient-friendly regimen modifications (PF) that has either reduced patient treatment cost and/or toxicity. Example: FolFox 6 Modified F, C, PF.
Risk Assessment:
Based on peer-reviewed literature, package insert, and published guidelines, all treatment regimens are analyzed for their emetogenic potential (low, medium, high) as well as their potential to induce Neutropenic Fever > 17 percent. The regimens included in the > 17 percent category include regimens identified as high risk in NCCN and ASCO guidelines, as well as intermediate risk regimens with one or more clinical risk factors. Example: Age > 64, prior chemotherapy, prior radiation therapy, and performance status > 1. Based on the advisory panel recommendation, Aloxi pre-populates the orders when a 5HT3 antiemetic is needed for moderate and high-risk regimens, and Zofran re-populates low risk regimens. Gcsf is indicated for pre-emptive cycle one inclusion in regimens with > 17 percent neutropenic fever risk per ASCO guidelines. Although Neulasta has been safely used in q4, q3, and q2 week regimens, the package insert is more limiting and therefore the advisory board defers to prescriber.
Alerts:
Alerts are provided for situations unique to specific therapeutic drugs. One alert is specific for drugs in which the prescriber may need to manually recalculate drug dosage. Creatinine elevations greater than 1.4 and bilirubin elevations greater than 1.4 fit into this category. A table is provided to assist dose recalculation. Additionally, any regimen containing carboplatin requires dosing calculation during each cycle. Another alert is for drugs that are associated with cardiotoxicity and require cardiac monitoring. Another alert is for drugs that may require additional pre-meds for side effect prevention. Lastly, regimens containing one or more drugs with which there is a greater than one percent risk of immediate or delayed hypersensitivity are also identified by a posted alert on the treatment summary page.
Informed Consent:
The provided informed consent has been in use in a practice in Georgia and was approved by legal counsel from the Medical Association of Georgia. Individual states and institutions may have specific requirements not met by this document.
Literature review:
The ChemoOrders.com Advisory Board performed a literature review for each disease and indication, and then summarized the findings in a brief statement that defines the treatment as a standard of care.
References:
Many peer-reviewed articles are published for each treatment regimen, often in multiple indications for each disease. The intent of the Advisory Board is to provide the single or few best articles that support the selected treatment for the identified disease and indication.
Document Design
Patient care summaries, flow sheets, and order documents were designed based on the input of our Advisory Board, and are consistent with documents with which practicing physicians are familiar.
Carboplatin
Carboplatin is calculated using the Calvert formula: (GFR + 25) * AUC = Carbo dose. Please note that the carboplatin dose must be recalculated each cycle/day.
Premedication Administration
Premedication administration instructions are the consensus of the Advisory Board.
Recommendation Based on Hepatic Function
Only drugs with formal dosage recommendations based on hepatic impairment are included in chart. Absence of drug on chart does not necessarily indicate that no adjustment is necessary.
Drug |
Recommendation Based on Hepatic Function |
Cyclophosphamide |
Reduce dose by 25% if tbili 3.0-5.0 mg/dL or SGOT > 180 mg/dL. Omit for tbili > 5.0 mg/dL |
Dactinomycin |
Reduce dose by 50% if tbili > 3.0 mg/dL |
Daunorubicin |
Total bilirubin 1.2—3 mg/dl: reduce recommended dose by 50%. |
Docetaxel |
Patients with bilirubin > upper limit of normal (ULN) should not receive docetaxel. In general docetaxel should not be given to patients with serum SGOT and/or SGPT > 1.5 times ULN with concurrent serum alkaline phosphatase > 2.5 times ULN |
Doxorubicin |
Total bilirubin 1.2—3 mg/dl: reduce recommended dose by 50%. |
Doxorubicin Liposomal |
Total bilirubin 1.2—3 mg/dl: reduce recommended dose by 50%. |
Etoposide |
Total bilirubin 1.5—3 mg/dl: Decrease etoposide dose by 50%. |
5-Fluorouracil |
Omit for tbili > 5.0 mg/dL |
Idarubicin |
Total bilirubin 1.2—3 mg/dl: reduce recommended dose by 50%. |
Imantinib |
The recommended starting dose is 400 mg/day for adults with mild or moderate hepatic impairment (total bilirubin 1.5—3 times the upper limit of normal and any ALT concentration). The recommended starting dose is 300 mg/day for adults with severe hepatic impairment (total bilirubin greater than 3 times the upper limit of normal and any ALT concentration). |
Interleukin-2 |
Hold the next dose for signs of hepatic failure including encephalopathy, increasing ascites, liver pain, hypoglycemia. Resume therapy once all signs of hepatic failure have resolved; however, it is recommended that further treatment for that course be discontinued. Consider starting a new course of treatment at least 7 weeks after cessation of adverse event. |
Methotrexate |
Psoriasis or rheumatoid arthritis patients with hepatic impairment due to alcoholism, cirrhosis, or other chronic liver disease should not receive methotrexate. Patients receiving high-dose methotrexate may have a prolonged half-life due to hepatic dysfunction and require additional monitoring and leucovorin therapy. |
Paclitaxel |
In general, dosage reductions of at least 50% are recommended in patients with moderate or severe hyperbilirubinemia or substantially increased serum transferase levels. The results of a study of patients with elevated serum bilirubin and/or liver enzymes indicate that the dose of paclitaxel should not exceed 50—75 mg/m2 IV over 24 hours or 75—100 mg/m2 IV over 3 hours. In addition, patients with AST > 2 times the upper limit of normal should not be treated with doses > 50 mg/m2 IV over 24 hours. |
Tretinoin |
It has been recommended if hepatic enzymes increase to > 5-times the upper limit of normal consideration should be given to temporarily discontinuing oral tretinoin therapy. |
Vinblastine |
Total bilirubin 1.5—3 mg/dl: reduce dose by 50%. |
Vincristine |
Total bilirubin 1.5—3 mg/dl: reduce dose by 50%. |
Vinorelbine |
Total bilirubin <= 2 mg/dl: No dosage adjustment required. |
References:
Clinical Pharmacology Copyright © 2007
Gold Standard Inc
Chu, Devita, Physician’s Cancer Chemotherapy Drug Manual, 2004
J Clin Oncol 1998;16:1811—9.
Recommendation Based on Renal Function
Only drugs with formal recommendations for dosage adjustments are included in chart. Absence of drug on chart does not necessarily indicate that no adjustment is necessary.
Drug |
Recommendation Based on Renal Function |
Bleomycin |
CrCl 36—50 ml/min: reduce dose by 25% |
Capecitabine |
CrCl >= 51 ml/min: No initial dosage adjustment is recommended. |
Cisplatin |
CrCl 46—60 ml/min: Decrease dose by 50%. |
Cyclophosphamide |
CrCl > 55 ml/min: No change needed. |
Etoposide |
CrCl 60—45 ml/min: Reduce etoposide dose by 15% |
Hydroxyurea |
Reduce dose by 80% if ClCr < 10 ml/min |
Interleukin-2 |
Serum creatinine > 4.5 mg/dl: hold dose until SCr < 4 mg/dl and fluid and electrolyte status are stable.Serum creatinine >= 4 mg/dl in the presence of severe volume overload, acidosis, or hyperkalemia: hold dose until SCr < 4 mg/dl and fluid and electrolyte status are stable. Persistent oliguria with urine output of <10 ml/hour for 16—24 hours with a rising SCr: hold dose until urine output > 10 ml/hour with a decrease of SCr > 1.5 mg/dl or normalization of SCr. |
Methotrexate |
CrCl >= 80 ml/min: no dosage adjustment needed. |
Mitomycin |
CrCl > 30—60 ml/min: Reduce dosage by 25%. |
Pemetrexed |
CrCl >= 45 ml/min: No dosage adjustment needed. |
Pentostatin |
CrCl > 60 ml/min: No dosage adjustment recommended. |
Procarbazine |
Although specific guidelines for dosage adjustments in renal impairment are not available; reduced doses are recommended to avoid excessive toxicity in patients with a BUN > 40 mg/dl and/or serum creatinine > 2 mg/dl. |
Streptozocin |
Omit if CrCl < 60 ml/min |
Topotecan |
When given in combination with cisplatin for the treatment of cervical cancer, topotecan therapy should only be initiated in patients with a serum creatinine <= 1.5 mg/dL. In the cervical cancer clinical trial, cisplatin was discontinued for a serum creatinine > 1.5 mg/dL. There are insufficient data available regarding the efficacy of continuing topotecan monotherapy after cisplatin discontinuation in cervical cancer patients. For other treatment regimens: |
Tretinoin |
Give a maximum of 25mg/m2 in the presence of renal dysfunction |
References:
Clinical Pharmacology Copyright © 2007 Gold Standard Inc
Chu, Devita, Physician’s Cancer Chemotherapy Drug Manual, 2004
Cancer Treat Rev 1995;21:33—64.