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Modified chemotherapy regimen shows promise for advanced anal squamous cell carcinoma
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A modified combination of docetaxel, cisplatin and fluorouracil conferred a long-lasting response and appeared well tolerated among patients with advanced anal squamous cell carcinoma, according to findings from a single-arm, multicenter, phase 2 study.
“Anal squamous cell carcinoma is still considered a rare disease, accounting for less than 3% of all gastrointestinal malignancies worldwide. However, the incidence of this cancer has been increasing substantially in the past few decades and it is estimated that it will continue to increase in the foreseeable future, reflecting its association with HPV infection,” Stefano Kim, MD, medical oncologist at University Hospital of Besançon, France, and colleagues wrote. “...When surgery is not possible, the current recommended treatment involves systemic chemotherapy. However, at present, evidence-based data defining the appropriate chemotherapy regimen are inadequate.”
The analysis included 66 adults (median age, 60.1 years; 82% women) with anal squamous cell carcinoma with either unresectable local recurrence or metastasis. Patients received either six cycles of standard therapy (75 mg/m² docetaxel and 75 mg/m² cisplatin on day 1; 750 mg/m² fluorouracil for 5 days, every 3 weeks; n = 36), or eight cycles of modified therapy (40 mg/m² docetaxel and 40 mg/m² cisplatin on day 1; 1,200 mg/m² fluorouracil for 2 days, every 2 weeks; n = 30).
PFS at 1 year following the first cycle of treatment served as the study’s primary endpoint. To meet this endpoint, a minimum of 11 patients had to be alive without progression at 1 year.
Researchers evaluated efficacy and safety in the intention-to-treat population, defined as all patients who received therapy and were evaluable for progression at the 1-year mark.
Thirty-one patients (47%) remained alive and progression free by 1 year.
Twenty-two patients (61%) who received the standard regimen had disease progression at the time of cut-off, compared with 18 (60%) of those who received modified therapy.
Overall, 70% of patients experienced at least one grade 3 or grade 4 adverse event, including 83% of patients assigned the standard regimen and 53% of those assigned the modified regimen.
Neutropenia was the most common grade 3 to grade 4 adverse event (standard therapy, n = 8; modified, n = 7), followed by diarrhea (standard, n = 9, modified, n = 3), asthenia (standard, n = 8; modified, n = 2), anemia (standard, n = 6; modified, n = 4), lymphopenia (standard, n = 3; modified, n = 5), mucositis (standard, n = 7) and vomiting (standard, n = 5; modified, n = 2).
No grade 4 nonhematologic adverse events or febrile neutropenia occurred among patients who underwent modified therapy; however, researchers reported three grade 4 nonhematologic adverse events and five cases of febrile neutropenia among patients who received standard treatment.
More patients assigned the standard regimen also experienced serious adverse events (n = 69 vs. 28).
In an accompanying editorial, Francesco Sclafani, MD, of the Royal Marsden NHS Foundation Trust in Sutton, United Kingdom, questioned whether physicians should treat all patients with advanced anal squamous cell carcinoma with modified docetaxel, cisplatin and fluorouracil chemotherapy based on these data.
“Unfortunately, the Epitopes-HPV02 trial does not answer the question of whether adding docetaxel to cisplatin and fluorouracil provides a significant and clinically meaningful incremental survival advantage without increasing the number of adverse events or compromising quality of life,” Sclafani wrote.
He added, however, that “Kim and colleagues should be commended for successfully completing their study despite the logistical difficulties of undertaking research in rare cancers.
“After being neglected for decades, advanced anal squamous cell carcinoma has finally become the focus of increasing investigation,” Sclafani continued. “Healthcare stakeholders are urged to keep this momentum going and to concentrate efforts to ultimately turn an orphan disease into a rare condition with robust, evidence-based treatment recommendations.” – by Andy Polhamus
Disclosures: The authors report no relevant financial disclosures. Sclafani is supported by National Institute for Health Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research.
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