ABSTRACT
BACKGROUND: The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). PATIENTS AND METHODS: Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. RESULTS: The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively. CONCLUSION: CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. EUDRA CT NO: 2007-007029-38.
Subject(s)
Anus Neoplasms/drug therapy , Anus Neoplasms/radiotherapy , Drug-Related Side Effects and Adverse Reactions/pathology , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Anus Neoplasms/pathology , Cetuximab , Chemoradiotherapy/adverse effects , Cisplatin/administration & dosage , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/classification , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Radiotherapy/adverse effectsSubject(s)
Rectal Neoplasms/radiotherapy , Rectum/pathology , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Capecitabine , Combined Modality Therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy/methods , ErbB Receptors/antagonists & inhibitors , Fluorouracil/analogs & derivatives , Fluorouracil/therapeutic use , Humans , Irinotecan , Organoplatinum Compounds/therapeutic use , Oxaliplatin , Preoperative Care , Radiotherapy Dosage , Radiotherapy, Conformal/adverse effects , Randomized Controlled Trials as Topic , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Rectal Neoplasms/metabolism , Rectal Neoplasms/pathology , Rectum/blood supply , Rectum/radiation effects , Survival Analysis , Treatment OutcomeABSTRACT
The study of 9 cases of agammaglobulinemia in the adult shows the classical symptomatology of these diseases. The evolutive study deals with too small a series to demonstrate statistically the superiority of the substitutive treatment over a simple chemo-therapeutic prevention of the infection, but nevertheless it shows : 1) that prognosis is bad only in cases of gross anatomical and physiological alterations and when they are the sole responsible for a fatal evolution; 2) that the substitutive treatment is only really efficient when given at high doses; the minimum dose of 250 mg per day seems advisable.
