GEMC

REPEAT EVERY 28 DAYS

For 6 cycles unless disease progression or unacceptable toxicity occurs

Other Supportive Care:

Doses should be modified according to the protocol by which the patient is being treated. 

Doses should not be re-escalated if they are reduced for non-hematological toxicities, febrile neutropenia or thrombocytopenic bleeding.

Table 1 - Day 1 of Cycle: 

* _{Do not start new cycle until ANC ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L and non-hematologic toxicity ≤ grade 2.  Discontinue if non-hematological toxicities require more than a 50% dose reduction from the starting dose.}

** _{except nausea/vomiting or alopecia}

Other treatment days within cycle:
 

Table 2 - Non-hematologic toxicities

* _{Treat only if non-hematologic toxicities recover to ≤ grade 2 and hematologic parameters are met on treatment day (Table 3). Discontinue if non-hematological toxicities require more than a 50% dose reduction from the starting dose.}

**_{except nausea/vomiting, alopecia}

Table 3 - Hematologic Toxicities:

* _{Treat only if above parameters are met on treatment day and non-hematologic toxicities ≤ grade 2.}

 Gemcitabine should be used with caution in patients with hepatic impairment (cirrhosis, hepatitis, alcoholism, metastases, etc.); initial dose reduction should be considered if the patient is treated, especially in hyperbilirubinemia.

Suggested:

Gemcitabine should be used with caution in patients with renal insufficiency. There is insufficient information from clinical studies to allow clear dose recommendations for this patient population. Clinical trials with cisplatin mandated CrCl ≥ 60mL/min. For patients with pre-existing renal insufficiency, the close monitoring for occurrence of hemolytic uremic syndrome is required.

Decreased clearance and increased half-life occurs with increasing age, however no dose adjustment is necessary.

Dosage based on Gender

Decreased volume of distribution and clearance are seen in women, however no dose adjustment is necessary.

Refer to gemcitabine drug monograph(s) for additional details of adverse effects

Refer to gemcitabine drug monograph(s) for additional details

• No specific drug interaction studies have been conducted.

• Monitor INR closely with concurrent warfarin use and adjust warfarin dose as needed, as gemcitabine may decrease metabolism and synthesis of clotting factors.

• Gemcitabine is a known radiosensitizer.

Refer to gemcitabine drug monograph(s) for additional details

Administration

• May dilute reconstituted drug in normal saline for IV infusion, resulting in a minimum final concentration of at least 0.1 mg/mL.

• Gemcitabine is for IV administration only and should be infused over 30 minutes.

• To prevent increased toxicity, avoid an infusion time of > 60 minutes or dosing more frequently than once weekly

Contraindications

• Patients who have a hypersensitivity to this drug or any of its components.

Other Warnings/Precautions

• Use with extreme caution in patients with compromised bone marrow reserve.

• Use with caution in patients with hepatic impairment (including concurrent liver metastases or a previous history of hepatitis, alcoholism or liver cirrhosis) and patients with renal impairment.

• Acute shortness of breath with a temporal relationship to gemcitabine injection administration may occur.

• Patients receiving concurrent radiation while receiving the full dose gemcitabine should be closely monitored for reactions. Exacerbation of radiation therapy toxicity including potentially life-threatening esophagitis and pneumonitis, particularly in patients receiving large volumes of radiotherapy have been observed.

Pregnancy/Lactation

• Gemcitabine is not recommended for use in pregnancy.  Adequate contraception should be used by both sexes during treatment, and for at least 6 months (general recommendation) after the last dose.

• Breastfeeding is not recommended.

• Fertility: Observed in animal studies

  • Decreased spermatogenesis and fertility in male mice.

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Suggested Clinical Monitoring

Hezel AF, Zhu AX.  Systemic therapy for biliary tract cancers.  Oncologist 2008;13(4):415-23.

Horgan AM, Amir E, Walter T, et al.  Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis.  J Clin Oncol 2012;30(16):1934-40. 

National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology:  Hepatobiliary Cancers.  V4.2017.

Neoptolemos JP, Moore MJ, Cox TF, et al.  Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial.  JAMA. 2012 Jul 11;308(2):147-56.

Ethun CG, Lopez-Aguiar AG, Pawlik TM, et al.  Adjuvant chemotherapy using gemcitabine for resected distal bile duct and ampullary cancers.  Hepatogastroenterology 2014;61(130):314-8.