Paclitaxel for Breast Cancer

Overseen By Cancer AnswerLine

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: CYP2C8 inducers, inhibitors

Disqualifiers: Hypersensitivity to paclitaxel, pregnant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 weeks

22 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this pharmacokinetics study is to compare the maximum concentration level of paclitaxel in patients with low/sarcopenic skeletal muscle area (SMA), at the end of a 2-3 hour paclitaxel infusion, to the maximum level in patients with normal SMA at the end of a standard 1-hour infusion with the goal of determining whether lengthening the infusion in patients with low/sarcopenic SMA normalizes the levels to those of patients with normal SMA.

Do I have to stop taking my current medications?

You may need to stop taking certain medications. The trial excludes participants who are taking moderate or strong inducers or inhibitors of CYP2C8, like rifampin or clopidogrel.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that affect the enzyme CYP2C8, like rifampin or clopidogrel, as they are not allowed during the trial.

What data supports the idea that Paclitaxel for Breast Cancer is an effective drug?

The available research shows that Paclitaxel, especially in its nanoparticle albumin-bound form (Abraxane), is effective for treating breast cancer. It has been approved by the US FDA for cases where other treatments have failed or the cancer has returned. In a study at M.D. Anderson Cancer Center, 14 out of 25 patients with metastatic breast cancer responded positively to Paclitaxel, with a median survival time of 20 months. Compared to Taxol, Abraxane has a shorter infusion time and does not require premedication, making it more convenient. Additionally, Paclitaxel is effective even in patients resistant to other drugs like anthracyclines. These findings suggest that Paclitaxel is a strong option for treating advanced breast cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Paclitaxel for breast cancer?

Paclitaxel has shown effectiveness in treating metastatic breast cancer, including cases resistant to other treatments, with studies indicating a significant response in patients. Nab-paclitaxel (Abraxane) is noted for its superior efficacy and less toxicity compared to traditional formulations, making it a favorable option for advanced breast cancer. ^{1 2 3 4 5}

What safety data is available for Paclitaxel in breast cancer treatment?

Paclitaxel, including its formulations such as nab-paclitaxel (Abraxane), has been evaluated in various clinical trials for breast cancer treatment. Nab-paclitaxel has shown less toxicity compared to traditional solvent-based paclitaxel (Taxol) and has a better safety profile, as demonstrated in phase III trials. It avoids the toxicities associated with the Cremophor vehicle used in solvent-based paclitaxel. Common side effects include febrile neutropenia, but treatment is generally well tolerated. A case of corneal disorder has been reported with nab-paclitaxel. Overall, paclitaxel has demonstrated safety and efficacy in both early-stage and metastatic breast cancer, with higher response rates and improved survival in some studies. ^{3 6 7 8 9}

Is paclitaxel safe for humans?

Paclitaxel, including its formulation as nab-paclitaxel (Abraxane), is generally considered safe for humans, with studies showing it is well tolerated in breast cancer treatment. It has fewer side effects compared to traditional formulations, though some side effects like febrile neutropenia (fever with low white blood cell count) and rare cases of corneal disorder have been reported. ^{3 6 7 8 9}

Is the drug Paclitaxel a promising treatment for breast cancer?

Yes, Paclitaxel is a promising treatment for breast cancer. It has shown significant effectiveness, especially in cases where other treatments have failed. The newer version, nab-paclitaxel, is even more effective and has fewer side effects, making it a better option for patients. It has been approved for use after other treatments haven't worked, and it can be used alone or with other drugs to improve results. ^{1 3 4 10 11}

How does the drug paclitaxel differ from other treatments for breast cancer?

Paclitaxel is unique because it is a cytotoxic agent that has been integrated into both single-agent and combination regimens for breast cancer, showing effectiveness even in anthracycline-resistant cases. A novel formulation, nab-paclitaxel, offers superior efficacy and less toxicity compared to traditional paclitaxel, as it does not require a toxic solvent, leading to safer administration and potentially better outcomes. ^{1 3 4 10 11}

Research Team

Daniel L Hertz, PharmD, PhD

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

This trial is for individuals with Stage 1-3 breast cancer who are planning or undergoing neoadjuvant, adjuvant, or curative intent chemotherapy with paclitaxel. Participants must have adequate organ function and an evaluable CT scan from the past year. Pregnant or nursing individuals, those with hypersensitivity to paclitaxel components, or those on certain CYP2C8 inhibitors/inducers cannot join.

Inclusion Criteria

Evaluable computed tomography (CT) scan within 1 year

My breast cancer is at stage 1, 2, or 3.

My organs are working well enough for chemotherapy.

Exclusion Criteria

I am not taking medications like rifampin or clopidogrel that strongly affect liver enzymes.

History of hypersensitivity reaction to paclitaxel or any components of paclitaxel that precludes continued treatment with standard dose and infusion length

Pregnant or nursing

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel infusion with adjusted duration based on skeletal muscle area

Up to 12 weeks

Infusion visits as per treatment schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Paclitaxel

Trial Overview The study tests if extending the infusion time of paclitaxel in patients with low skeletal muscle area can normalize drug concentration levels compared to those with normal muscle area receiving a standard infusion duration.

Participant Groups

Group I: Low SMA (5120 - 7310 mm^2) and Sarcopenic SMA (<5120 mm^2) Experimental Treatment 1 Intervention

Adjusted paclitaxel infusion time during only one dose; standard paclitaxel infusion time for all other doses.

Group II: Normal SMA (>7310 mm^2) Active Control 1 Intervention

Standard paclitaxel infusion time.

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Findings from Research

In a phase II study involving 25 patients with metastatic breast cancer, paclitaxel demonstrated significant efficacy, with 14 patients achieving a major response and a median survival time of 20 months.

Paclitaxel remains effective even in patients who have undergone multiple prior chemotherapy regimens, including those resistant to anthracyclines, although combination therapies can lead to serious side effects like neutropenic fever and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. Hortobagyi, GN., Holmes, FA., Ibrahim, N., et al.[2015]

Paclitaxel (Taxol) is a highly effective drug for treating breast cancer, particularly in patients with HER2-positive tumors, suggesting that HER2 status could guide treatment decisions.

Future research aims to refine treatment strategies by identifying specific criteria for paclitaxel use, potentially improving outcomes by avoiding unnecessary treatment in patients with lower likelihoods of benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions of paclitaxel-based therapy of breast cancer. Gianni, L.[2015]

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

Abraxane® demonstrated a significantly shorter drug delivery time (84 minutes) and lower overall costs (US$59 per dose) compared to Taxol® (282 minutes and US$254 per dose), making it a more efficient treatment option for advanced breast cancer.

Patients receiving Abraxane® experienced fewer acute adverse drug reactions (8.3%) compared to those treated with Taxol® (33.3%), indicating a potentially safer profile for Abraxane® in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane® versus Taxol® for patients with advanced breast cancer: A prospective time and motion analysis from a Chinese health care perspective. Dranitsaris, G., Yu, B., Wang, L., et al.[2016]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

Nab-paclitaxel, a novel formulation of paclitaxel, has shown higher response rates and a better safety profile compared to conventional paclitaxel in a phase III clinical trial, making it a promising option for breast cancer treatment.

This formulation allows for higher doses to be administered over shorter infusion times without the need for special equipment or pre-medications, and it is now approved for use in patients with metastatic breast cancer after prior chemotherapy failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer. Vishnu, P., Roy, V.[2021]

Paclitaxel has shown promising efficacy in treating stage IV breast cancer, with overall response rates ranging from 44% to 62% in phase II trials, indicating it can be an effective option for patients with limited prior therapy.

The treatment is generally well tolerated, with febrile neutropenia being the most common side effect, and it has demonstrated safety and efficacy even in patients with extensive prior therapy, achieving response rates of 36% in those with two prior treatments and 21% in those with three or more.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent use of Taxol (paclitaxel) in breast cancer. Seidman, AD.[2016]

A 55-year-old woman developed corneal disorders, including blurred vision and epithelial defects, after treatment with nab-paclitaxel, indicating that this microtubule inhibitor can cause significant ocular side effects.

After discontinuing nab-paclitaxel, her corneal condition improved dramatically, suggesting that the drug was the likely cause of her symptoms, although the potential contribution of other medications like trastuzumab and pertuzumab should also be considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Case of a Corneal Disorder after Breast Cancer Treatment with Nab-paclitaxel]. Hosotani, Y., Morimatsu, T., Takata, M., et al.[2016]

Nanoparticle albumin-bound paclitaxel (ABI-007, Abraxane) is a safer alternative to conventional paclitaxel for breast cancer treatment, as it eliminates the need for toxic solvents and premedication.

Recent trials indicate that ABI-007 is well tolerated and offers superior outcomes compared to standard paclitaxel, including higher response rates, longer time to tumor progression, and extended survival in patients with metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. Moreno-Aspitia, A., Perez, EA.[2023]

Paclitaxel (Taxol) is a significant new chemotherapy drug for breast cancer, showing promise in both single-agent and combination treatments.

Ongoing research at Memorial Sloan-Kettering Cancer Center aims to optimize the use of paclitaxel in various treatment settings, including metastatic and adjuvant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. Seidman, AD., Hudis, CA., Fennelly, D., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Future directions of paclitaxel-based therapy of breast cancer. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Abraxane® versus Taxol® for patients with advanced breast cancer: A prospective time and motion analysis from a Chinese health care perspective. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of nab-Paclitaxel in the Treatment of Patients with Breast Cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Single-agent use of Taxol (paclitaxel) in breast cancer. [2016]

9. Japan pubmed.ncbi.nlm.nih.gov

[A Case of a Corneal Disorder after Breast Cancer Treatment with Nab-paclitaxel]. [2016]

10. England pubmed.ncbi.nlm.nih.gov

Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer. [2015]