Label Update for Capecitabine Expands and Updates Indications

The FDA has approved updated labeling for capecitabine (Xeloda) tablets, making it the first agent to be granted a labeling update under Project Renewal.¹

Under the updated label, capecitabine is now approved for the adjuvant treatment of patients with stage III colon cancer as monotherapy or in combination with a chemotherapy regimen. Additionally, the agent is approved for the perioperative treatment of adults with locally advanced rectal cancer as a part of chemoradiotherapy and for patients with unresectable or metastatic colorectal cancer, either as a monotherapy or as a component of a combination chemotherapy regimen. In the breast cancer space, capecitabine is approved for patients with advanced or metastatic breast cancer as a single agent if anthracycline- or taxane-containing chemotherapy is not indicated, as well as in combination with docetaxel following disease progression on anthracycline-containing chemotherapy.

For patients with unresectable or metastatic gastric, esophageal, or gastroesophageal junction (GEJ) cancer capecitabine is now indicated as part of a combination chemotherapy regimen and as a part of a combination regimen for patients with HER2-overexpressing disease who have not received prior treatment for metastatic disease. The agent is also indicated as a component of a combination chemotherapy regimen for the adjuvant treatment of adult patients with pancreatic adenocarcinoma.

The Oncology Center of Excellence initiated Project Renewal with the ultimate aim of updating labeling information for oncology agents, especially those that are older and commonly prescribed, by evaluating relevant scientific evidence from published literature. The program utilizes external oncology experts and early-career scientists to review the existing published literature.^1,2

The initiative was conceived to address outdated labeling that exists on many oncology agents and applying new information that comes to light in the post-marketing setting that could potentially warrant labeling changes and indication updates. The key goals of Project Renewal are to: develop repeatable processes, use published data, engage with the oncology community, and foster educational experiences.

The recent labeling update also revised and updated the dosing regimen for multiple indications, including allowing for a reduced starting dose for patients with metastatic breast cancer. Under the revision, severe renal impairment was removed as a contraindication, information on risks from exposure to crushed tablets was added in the warnings and precautions section, and more information was given regarding the relationship between treatment with capecitabine and dihydropyrimidine dehydrogenase deficiency. The FDA also updated and revised clinical pharmacology information, the Patient Counseling Information section, and thePatient Information document.¹

According to the updated label, capecitabine can be given for the adjuvant treatment of patients with colon cancer as monotherapy at a dose of 1,250 mg/m² twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles or at a dose of 1000 mg/m² twice daily for the first 14 days of each 21-day cycle for a maximum of 8 cycles in combination with oxaliplatin 130 mg/m². For the perioperative treatment of rectal cancer, the agent should be administered at a dose of 825 mg/m² twice daily or 1250 mg/m² twice daily for patients who are being treated with concomitant radiation therapy or without radiation therapy, respectively.³

Patients with unresectable or metastatic colorectal cancer can be given capecitabine 1250 mg/m² for the first 14 days of each 21-day cycle as monotherapy or at a dose of 1000 mg/m² twice daily for the first 14 days of each 21-day cycle when used in combination with oxaliplatin 130 mg/m² given on day 1 of each cycle. In pancreatic cancer, the agent can be administered at a dose of 830 mg/m² twice daily for the first 21 days of each 28-day cycle for a maximum of 6 cycles in combination with gemcitabine 1,000 mg/m² given on days 1, 8, and 15 of each cycle.

Patients with advanced or metastatic breast cancer can be treated with capecitabine monotherapy at a dose of either 1,000 mg/m² or 1,250 mg/m² twice daily orally for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity. The agent can also be administered at either dosing schedule in combination with docetaxel 75 mg/m² on day 1 of each cycle in this patient population.

Finally, capecitabine is indicated at a dose of 625 mg/m² twice daily on days 1 to 21 of each 21-day cycle for a maximum of 8 cycles in combination with platinum-containing chemotherapy or at a dose of 850 mg/m² or 1,000 mg/m² twice daily for the first 14 days of each 21-day cycle until disease progression or unacceptable toxicity in combination with oxaliplatin 130 mg/m² on day 1, for patients with unresectable or metastatic GEJ cancer. Patients with HER2-overexpressing metastatic GEJ cancer can be treated with the agent at a dose of 1000 mg/m² twice daily for the first 14 days of each 21-day cycle.

References

1. FDA approves updated drug labeling including new indications and dosing regimens for capecitabine tablets under Project Renewal. News release. FDA. December 14, 2022. Accessed December 16, 2022. bit.ly/3HH2AY8
2. Project renewal. Updated February 15, 2022. Accessed December 16, 2022. bit.ly/3BGeKN6
3. Xeloda. Prescribing information. Genentech; 2022. Accessed December 16, 2022. bit.ly/3YxAJzU