Paclitaxel

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Paclitaxel is a chemotherapeutic agent used as therapy for several types of cancer. It has a long list of both approved and off-label malignancies for which it is used as both a primary agent and in conjunction with other medications. Indicated cancers include breast, ovarian, bladder, lung, prostatic, melanoma, esophageal, Kaposi sarcoma, and other solid tumors. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of paclitaxel so providers can direct patient therapy to optimal outcomes in cancers where paclitaxel has benefit.

Objectives:

  • Identify the mechanism of action for paclitaxel.
  • Describe the potential adverse effects of paclitaxel.
  • Summarize the malignancies for which paclitaxel is indicated, both approved and off-label.
  • Review the importance of improving care coordination among the interprofessional team to enhance care delivery for patients who can benefit from chemotherapy with paclitaxel.

Indications

FDA Approved Indications

  • Adjuvant treatment for node-positive breast cancer [1]
  • Treatment of metastatic breast cancer after failure of combination chemotherapy that included an anthracycline [2]
  • Treatment of metastatic breast cancer that relapsed within six months of adjuvant chemotherapy that included an anthracycline [3][4]
  • Treatment of AIDS-related Kaposi sarcoma (second line)[5]
  • Treatment of non-small cell lung cancer in combination therapy with cisplatin in patients who are not candidates for surgery and/or radiation therapy[6]
  • Treatment of ovarian cancer in combination with cisplatin[7][8]
  • Subsequent therapy for the treatment of advanced ovarian cancer in combination with cisplatin[9][10]

Non-FDA Approved Indications

  • Treatment of metastatic or advanced bladder cancer in combination therapy with gemcitabine[11][12]
  • Treatment of advanced cervical cancer in combination with topotecan, bevacizumab, and/or cisplatin[13][14][15]
  • Preoperative management of esophageal and gastric cancers in combination with carboplatin and radiation therapy[16]
  • Treatment of advanced head and neck cancer in combination with cisplatin[17]
  • Neoadjuvant treatment in penile cancer with bulky regional lymph node metastases[18]
  • Treating relapsed or refractory small-cell lung cancer[19][20]
  • Treatment of advanced or unresectable angiosarcoma[21][22]
  • Treatment of relapsed or refractory testicular germ cell tumors in combination with gemcitabine and oxaliplatin or ifosfamide and cisplatin[23][24][25]
  • Treatment of advanced thymoma/thymic carcinoma in combination with carboplatin[26]
  • Treatment of unknown primary adenocarcinoma in combination with carboplatin and/or etoposide [27][28]
  • Treatment of endometrial carcinoma[29]
  • Treatment of metastatic or unresectable esophageal cancer[30]
  • Treatment of metastatic or unresectable gastric cancer[31]
  • Treatment of melanoma[32]
  • Treatment of anaplastic thyroid cancer[33]

Mechanism of Action

Paclitaxel is an antimicrotubule agent. It promotes the assembly of microtubules by enhancing the action of tubulin dimers and stabilizing current microtubules while inhibiting their disassembly. Due to the stability of the microtubules, the late G2 phase stops, and cell replication becomes inhibited. Paclitaxel may also distort mitotic spindles causing the chromosomes to break.[34]

Administration

Paclitaxel is available as an IV formula infused over 3 to 24 hours, depending on the indication or protocol. Certain off-label protocols use a 1-hour infusion, as well as off-label intraperitoneal use. Paclitaxel infusion should be through a 0.22-micron in-line filter and polyethylene-lined administration set (non-PVC).[35] If the drug is part of a combination chemotherapy regimen, the order may vary by regimen, and it is important to refer to a protocol for the recommended sequence. Patients may also be premedicated with dexamethasone, diphenhydramine, cimetidine, or ranitidine before the infusion.[36][37][38] Because paclitaxel is such a potent irritant, care to avoid extravasation must be taken. Caution with needle and catheter position is essential during the administration of the medication.  

Adverse Effects

Paclitaxel has a black box warning for hypersensitivity reactions and bone marrow suppression. Patients should be premedicated with corticosteroids, diphenhydramine, and H2 antagonists prior to infusion to avoid anaphylaxis and severe hypersensitivity reactions. The recommendation is for dexamethasone at 20 mg IV or orally (10 mg if the patient has advanced HIV) 12 and 6 hours before the paclitaxel dose. Diphenhydramine should be administered 30 to 60 minutes before the dose at 50 mg IV. Cimetidine 300 mg, famotidine 20 mg, or ranitidine 50 mg would all be appropriate choices to be administered IV at 30 to 60 minutes before the dose. Severe hypersensitivity reactions would include dyspnea requiring bronchodilators, hypotension requiring treatment, angioedema, and/or generalized urticaria. In cases of serious hypersensitivity reaction, stop the infusion and discontinue paclitaxel. Minor hypersensitivity reactions do not require treatment to be interrupted or discontinued. Minor hypersensitivity reactions would include flushing, dyspnea, hypotension, skin reactions, or tachycardia.[39][40]

The most prevalent side effects of paclitaxel are alopecia, nausea and vomiting, mucositis, neutropenia, leukopenia, anemia, hypersensitivity reactions, arthralgia, myalgia, and weakness. Peripheral neuropathy is another common side effect, and patients with preexisting neuropathies may have an increased risk. The dose should be reduced by 20% for patients who develop severe neuropathy.[41]

Other less common side effects include flushing, edema, hypotension, skin rash, stomatitis, thrombocytopenia, hemorrhage, increased serum alkaline phosphatase and AST, local injection site reaction, increased serum creatinine, along with many more. Injection site reactions are generally mild (erythema, tenderness, skin discoloration, or swelling) and tend to occur more often with an extended infusion duration, for example, 24 hours. It is worth noting that delays of injection site reactions can extend from 7 to 10 days. Patients may also experience infusion-related hypotension, bradycardia, and/or hypertension. Due to that concern, the recommendation is that the patient's vital signs undergo frequent monitoring, especially during the first hour of infusion.[42] 

Contraindications

Due to the black box warning for hypersensitivity reactions and bone marrow suppression, paclitaxel should not be given to patients who have had a severe hypersensitivity reaction with paclitaxel, patients with solid tumors who have a baseline neutrophil count of fewer than 1500 cells/mm^3, or patients with AIDS-related Kaposi sarcoma if the baseline neutrophil count is less than 1000 cells/mm^3. Bone marrow suppression is dose-dependent and is a dose-limiting toxicity. If it occurs, future doses should be reduced by 20% for severe neutropenia and consider supportive therapy (growth factor treatment).[43]

Monitoring

The infusion site should be monitored for extravasation. If it occurs, stop the infusion immediately and disconnect, but leave the needle/cannula in place. The extravasated solution should be gently aspirated, but it is crucial not to flush the line. Remove the needle/cannula, initiate the antidote, remove that needle/cannula, and elevate the extremity. The data conflicts over whether to use warm or cold compresses.[44] Patients should also be monitored for a severe hypersensitivity reaction. Although every patient should be premedicated to prevent one from happening, some patients may still experience one which would warrant treatment discontinuation. 

Toxicity

Hyaluronidase is the antidote for paclitaxel and is commonly used for the treatment of extravasation. If the needle/cannula is still in place, administer 1 to 6 mL into the existing IV line. If the needle/cannula is no longer inserted, the hyaluronidase may be injected subcutaneously clockwise around the area of extravasation. This procedure may be repeated several times over the next 3 to 4 hours.[45]

Enhancing Healthcare Team Outcomes

Successful interprofessional teamwork and communication assure that all patients receive their appropriate dose and regimen based on FDA guidelines or hospital protocol. Oncologists should thoroughly evaluate the patient and select an appropriate treatment regimen based on guidelines and patient-specific factors. Nurses should be made aware of the signs and symptoms of hypersensitivity reactions to paclitaxel, along with extravasation management. Pharmacists should examine the patient’s current and complete drug regimen and make sure there are no interactions, as paclitaxel has many that could make treatment modifications necessary. These are just a few examples of healthcare professionals that may have responsibilities for patients taking paclitaxel. Naturally, roles tend to overlap in various health professions, but every healthcare professional provides a vital role that benefits the patient to the highest degree. [Level 5]

Details

Author

Ayoola O. Awosika

Author

Maela C. Farrar

Editor:

Tibb F. Jacobs

Updated:

7/19/2023 5:07:22 PM

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