Docetaxel Promising in Early Breast Cancer, Advanced Head and Neck Cancer

Two studies published recently in the Journal ofClinical Oncology showed promising response rates for docetaxel (Taxotere)-basedtherapy over existing therapies for several types of cancer.

Early Use in Breast Cancer

The results of a study (J Clin Oncol 20:1456-1466, 2002) support the additionof docetaxel to neoadjuvant chemotherapy for breast cancer. The study in womenwith large (³ 3 cm) or locally advanced breast cancer showed that those whoreceived docetaxel following anthracycline-based chemotherapy achieved a bettertumor response rate than did those given the anthracycline-based regimen alone.Treatment with an anthracycline-based regimen is currently the standard of carein the neoadjuvant setting.

The study, conducted at the University of Aberdeen in the United Kingdom,found that patients who responded to four cycles of neoadjuvant chemotherapywith the anthracycline-based regimen CVAP (cyclophosphamide [Cytoxan, Neosar],vincristine, doxorubicin [Adriamycin], prednisolone), followed by four cycles ofdocetaxel, experienced a higher clinical response rate (94% vs 66%) and a highercomplete pathologic response rate (34% vs 16%) than patients given fouradditional cycles of the anthracycline regimen.

"In localized breast cancer, the goal of chemotherapy given prior tosurgery is to reduce the size of the tumor, thus increasing the likelihood ofbreast conservation and improving survival," said Steven Heys, professor ofsurgical oncology and nutritional oncology, University of Aberdeen. "Inthis study, patients given docetaxel in addition to an anthracycline-basedchemotherapy experienced a better response rate in terms of tumor reduction,which suggests that patients given docetaxel are less likely to have to undergomastectomy following completion of the chemotherapy. These results stronglysupport the addition of docetaxel to neoadjuvant chemotherapy in the treatmentof breast cancer."

Survival Benefit Demonstrated

Additional data from this study were presented at the 24th Annual San AntonioBreast Cancer Symposium. According to data presented there, patients whoreceived the neoadjuvant docetaxel-containing regimen lived significantly longerthan patients who did not receive docetaxel. Patients in the CVAP/docetaxel armachieved a 97% 3-year survival rate, compared to 84% in patients in the CVAP/CVAParm. In addition, the disease-free survival rate at 3 years was 90% in thedocetaxel arm, compared with 77% in patients who did not receive docetaxel.

While these survival data are encouraging, Dr. Heys added, "it isimportant to keep in mind that these are preliminary data and that largerstudies will be needed to confirm their significance."

The study included 104 patients with large or locally advanced breast cancerwho demonstrated a clinical response after four initial cycles of CVAPchemotherapy. Of those patients, 52 were randomized to receive four furthercycles of CVAP, and 52 were randomized to receive four cycles of docetaxel. Anadditional 55 patients enrolled in the trial failed to demonstrate a response tothe initial CVAP therapy and were treated with four cycles of docetaxel. Ofthese patients, 55% (n = 26) achieved a clinical response following the fourcycles of docetaxel.

Significantly fewer hematologic side effects were experienced by women in thedocetaxel arm of the study. Patients who received docetaxel required fewer dosereductions due to hematologic toxicity than did patients who received theanthracycline-based regimen.

Use in Advanced Head and Neck Cancer

A separate study published in the same issue of the Journal of ClinicalOncology (20:1593-1599, 2002) showed that a combination of docetaxel andcisplatin is an effective treatment for patients with recurrent or incurablehead and neck cancer. The phase II multicenter study was designed to assess theantitumor activity and toxicity of docetaxel, 75 mg/m² as a 1-hour infusion,plus cisplatin, 75 mg/m² as a 30-minute infusion, in patients with recurrent orincurable squamous cell carcinoma of the head and neck. Treatment cycles wererepeated every 21 days.

Patients given the docetaxel/cisplatin combination achieved a 40% overallresponse rate and a median survival of 9.6 months. The current standardtreatment for patients with recurrent squamous cell carcinoma of the head andneck is cisplatin-based combination therapy with fluorouracil (5-FU), which isassociated with significant mucosal toxicity and a longer administration time.Investigators concluded that the doectaxel/cisplatin combination has anacceptable safety profile and may offer advantages over the current standardtreatment.

Phase III Trial Under Way

"The overall response rate and median survival demonstrated with thedocetaxel/cisplatin combination is somewhat higher than what we’ve seen withthe current standard regimen," said Bonnie S. Glisson, MD, professor ofmedicine, M. D. Anderson Cancer Center, Houston. "In addition, we saw lessmucosal toxicity and a shorter, more convenient administration than we see withthe standard cisplatin/5-FU combination regimen. These are important findingsthat we hope to confirm in a larger, phase III comparative trial, which isalready under way."

Although the incidence of severe neutropenia was high (80%), only 17% ofpatients experienced severe infection associated with grade 4 neutropenia orrequired intravenous antibiotics for neutropenic fever without documentedinfection.