Taxotere, a chemotherapy drug used primarily for breast cancer treatment, has come under fire for a distressing, unexpected side effect— permanent alopecia.
Taxotere MDL In Louisiana
As of October 2017, more than 1,500 Taxotere lawsuits are consolidated in the US District Court for the Eastern District of Louisiana. Under the guidance of District Judge Kurt D. Engelhardt, hundreds of women have seen their hair loss cases move through pre-trial proceedings as members of a Multi-District Litigation, or MDL. A legal structure that allows multiple similar lawsuits to come together in a single court, MDL has pushed the pace of the Taxotere litigation, enabling defendant Sanofi-Aventis to focus on one jurisdiction, rather than courts across the country.
What’s next? After all of the evidence is gathered, and the legal arguments have been honed, the cases will be ready for trial. Judge Engelhardt has already scheduled four of these trials for 2019:
- Monday, January 28, 2019
- Monday, April 8, 2019
- Monday, July 15, 2019
- Monday, November 4, 2019
These four initial trials are known as “bellwether” trials. Real plaintiffs. Real juries. Real evidence and arguments and, at the end, a real verdict. But bellwether trials are far more than that. After these four cases have been decided, the plaintiffs and Sanofi-Aventis will have gained a real-world understanding of what their case is worth. In turn, the judgments will come to affect ongoing settlement negotiations.
Cancer Drug Leaves Women With Permanent Alopecia
Though it’s widely-known that chemotherapy frequently causes hair loss, this side effect is almost always temporary, and patients typically see hair growth restored only months after treatment has ended. Permanent hair loss used to be practically unheard-of among chemotherapy patients.
But some women who took Taxotere have yet to see regrowth a decade post-treatment. Worse yet, medical research suggests Taxotere permanent hair loss is far from rare, with current risk estimates ranging from 3% to 15%.
Patients in the U.S. have started filing Taxotere lawsuits against Sanofi, the drug’s manufacturer, accusing the corporation of carelessly omitting or even actively concealing permanent hair loss risks. According to these lawsuits, by failing to provide proper side effect warnings, Sanofi prevented patients from seeking out lower-risk competitor drugs that may have spared their hair and gained billions of dollars in increased revenues at the expense of patient well-being.
What Is Taxotere?
Taxotere is a chemotherapy drug manufactured by Sanofi, the world’s 5th-largest pharmaceutical company, which is headquartered in France. Taxotere’s active ingredient, docetaxel, is approved in the US, Canada and throughout Europe for the treatment of several types of cancer.
Uses Of Taxotere
The FDA initially approved Taxotere on May 14, 1996, for treating locally advanced or metastatic breast cancer in cases where other types of chemotherapy have proven ineffective. The drug was later approved for a number of additional indications, including:
- treatment of locally advanced or metastatic non-small cell lung cancer in cases where platinum-based chemotherapy has failed (December 23, 1999)
- first-line chemotherapy treatment for unresectable, locally advanced, or metastatic non-small cell lung cancer (November 27, 2002)
- treatment of metastatic, hormone-refractory prostate cancer in combination with prednisone (May 19, 2004)
- adjuvant therapy for operable, node-positive breast cancer in conjunction with doxorubicin and cyclophosphamide (August 18, 2004)
- treatment of advanced gastric adenocarcinoma in combination with cisplatin and fluorouracil in patients who had not previously received chemotherapy for the advanced form of the disease (March 22, 2006)
- first-line treatment for inoperable, locally advanced squamous cell carcinoma of the head and neck (October 17, 2006)
Taxotere is commonly used in combination with other chemotherapy drugs, but it can also be used by itself (as a “monotherapy”). One cycle of the drug typically consists of an intravenous infusion administered over a one-hour session followed by a 3-week rest period. Dosage and number of cycles are assigned according to a number of factors, including cancer type, stage of cancer, and individual sensitivity to the drug’s side effects.
How It Fights Cancer
Docetaxel,the active compound in Taxotere, belongs to the taxane class of chemotherapy agents. Taxanes are plant-based chemicals classified as “mitotic inhibitors,” which disrupt the process of mitosis (or cell division) and thus prevent cancer cells from reproducing, as well as killing existing cancer cells.
In particular, taxanes target microtubules, thread-like structures that play a pivotal role in mitosis and also serve other vital cell functions such as skeletal support and transport within the cell.
In order to function properly, microtubules must be able to constantly lengthen and shorten themselves to achieve “dynamic instability,” a balance between growing and shrinking phases. Docetaxel throws off this vital balance by binding to microtubules in such a way that prevents them from shortening.
Discovery And Development
Taxotere was discovered during the development of its leading competitor drug, Bristol-Myers Squibb’s Taxol, a closely-related taxane chemotherapy drug that was first approved by the FDA in 1992.
Taxol’s active ingredient, paclitaxel, was first isolated from the inner bark of the rare Pacific Yew tree (Taxus brevifolia) in 1971, and by the late 70’s, scientists discovered that it exhibited a new, unique type of anti-cancer activity. But harvesting enough of the compound to make it into an effective chemotherapy drug would be harmful to the environment, requiring about 3 trees to be cut down to treat just one patient. Though the potential environmental impact of Taxol production sparked public controversy, the medical community couldn’t simply abandon a drug that held such immense potential for cancer treatment.
So a considerable amount of research was focused on developing new production methods as well as exploring related compounds. One of these was docetaxel, Taxotere’s active ingredient, discovered by Pierre Potier, a French researcher working for RhonePoulenc, a corporation which would later become part of Sanofi. Though Docetaxel was found to be roughly twice as potent as paclitaxel, its production didn’t require chopping down trees, as the necessary extracts come from the leaves rather than the bark of the common European Yew (Taxus baccata).
Thankfully, the environmental impact of producing both docetaxel and paclitaxel has been greatly reduced after researchers developed semi-synthetic methods of manufacturing them. For taxanes, semi-synthetic production, in which scientists take a “pre-cursor” molecule from a natural extract that already significantly resembles the desired product and then finish the rest of the transformation in the lab, has proven to be a much more cost-effective alternative to both the environmentally harmful approach of relying on harvested extracts and the impractical total synthesis route (that is, starting “from scratch” in the lab, which is very inefficient and expensive for large complicated molecules like taxanes).
An Improvement Over Taxol?
Now that Taxotere no longer has the advantage of being easier to produce and better for the environment than Taxol, healthcare professionals can instead focus on the drug’s effectiveness and side effect considerations when weighing options for a chemotherapy regimen. Predictably, Sanofi advertises Taxotere as a better choice than Taxol, but what does the research say?
Higher Overall Survival With Weekly Taxol
A 2007 study published in the New England Journal of Medicine found that women with “axillary lymph node–positive or high-risk lymph node–negative breast cancer” experienced higher disease-free survival and overall survival rates on a weekly paclitaxel regimen than those on an every 3 weeks paclitaxel or docetaxel regimen. The researchers also noted that patients suffered a much higher rate of “grade 3 or 4 toxic effects” on docetaxel (71% for every 3 weeks and 45% for weekly) than on paclitaxel (30% for every 3 weeks and 28% for weekly).
“No Overall Gain” From Adding Taxotere
A randomized, controlled 2009 study published in the Lancet found that adding Taxotere to standard anthracycline chemotherapy offers no benefit to patients with early-stage breast cancer. 4,000 patients in the UK and Belgium were randomly assigned to receive either a standard FEC or CMF regimen by itself or along with Taxotere. The disease-free survival rates at 5 years only increased by 0.6% to 2.5% with the addition of docetaxel, which the authors judged as “not clinically worthwhile.” Again, there was a “significantly greater” ratio of patients experiencing grade 3 or 4 toxicities in the docetaxel group than in the control group.
Studies On Hair Loss
Taxotere was initially rejected by the FDA over toxicity concerns. Now, many critics believe that Taxotere’s higher potency is responsible for increased toxicity, leading to a greater number of side effects as well as higher side effect severity in comparison to the less potent Taxol.
Permanent hair loss, a particularly dreaded side effect that was once considered extremely rare in chemotherapy, is increasingly linked to Taxotere in medical research.
Persistent Alopecia In 6% Of Patients
Taxotere was strongly indicated as a cause of permanent alopecia in a 2006 study performed by Dr. Scot Sedlacek from the Rocky Mountain Cancer Centers in Denver. Sedlacek set out to shed light on Persistent Significant Alopecia (PSA) in breast cancer patients receiving adjuvant chemotherapy. Though PSA was thought to be exceedingly rare among chemo patients, Sedlacek had seen a “small but significant” number of affected patients over his years as a practicing oncologist.
Collecting data on nearly 500 patients whom he’d treated personally over a period of 11 years (from Jan. 1994 to Dec. 2004), Sedlacek grouped patients by the adjuvant chemotherapy regimen they were assigned:
- Group A. Doxorubicin regimen without a taxane (258 patients)
- Group B. Doxorubicin plus paclitaxel (126 patients)
- Group C. Doxorubicin plus docetaxel (112 patients)
In order to ensure that cases of persistent alopecia could be accurately diagnosed, only patients with at least one year of follow-up data were included in the study. The average time elapsed since the last dose of chemotherapy received was 4 years, with a range of 19 to 85 months.
Is Permanent Hair Loss Confined To Taxotere?
Sedlacek found that 6% of Group C participants developed PSA, which he defined as the loss of more than 50% of pre-chemo coverage lasting longer than 6 months.
On the other hand, none of the patients treated with docetaxel-free regimens suffered from PSA. The patients with PSA coped with their condition by wearing wigs and described the appearance of their hair loss as similar to male pattern baldness. Sedlacek concluded that Taxotere is a possible cause of permanent hair loss. Noting that alopecia is among the most dreaded side effects of chemotherapy for patients, he urges doctors and patients to consider the risks of the “emotionally devastating” side effect when deciding on the optimal adjuvant treatment plan.
More Taxotere Resources