Prasert Lertsanguansinchai

Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial

PURPOSE This is a prospective, Phase III multicenter randomized trial to assess the effectiveness of concurrent intravenous mitomycin C, oral 5-fluorouracil (5-FU), and radiotherapy (RT) in locally advanced carcinoma of the cervix. METHODS AND MATERIALS Between January 1988 and November 1994, 926 patients with locally advanced carcinoma of the cervix, FIGO Stage IIB-IVA, were entered into this study. The patients were randomized into four arms, as follows: Arm 1: conventional RT; Arm 2: conventional RT and adjuvant chemotherapy; Arm 3: conventional RT plus concurrent chemotherapy; Arm 4: conventional RT plus concurrent chemotherapy and adjuvant chemotherapy. Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2) was given on Days 1 and 29, and oral 5-FU at 300 mg/day was administered on Days 1-14 and 29-42 during RT. Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks, with a 2-week rest every 6 weeks. Six centers participated in the trial. RESULTS The median follow-up time was 89 months. Acute side effects were generally higher in concurrent arms, but most of the patients tolerated the treatment well. Bone marrow toxicity was also higher in concurrent arms. The 5-year actuarial disease-free survival (DFS) was 48.2%, 54.1%, 64.5%, and 59.7% for arms 1, 2, 3, and 4, respectively. The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm. The local recurrence was 25.5%, 20.6%, 14.3%, and 17.6% for arms 1, 2, 3, and 4, respectively. The metastatic rates were not significantly different in all four arms. At the time of analysis, there were no increases in late side effects, especially in gastrointestinal and genitourinary systems. CONCLUSIONS Concurrent chemotherapy, mitomycin C, and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix.

Asian expert recommendation on management of skin and mucosal effects of radiation, with or without the addition of cetuximab or chemotherapy, in treatment of head and neck squamous cell carcinoma

With increasing numbers of patients with unresectable locoregionally advanced (LA) head and neck squamous cell carcinoma (HNSCC) receiving cetuximab/radiotherapy (RT), several guidelines on the early detection and management of skin-related toxicities have been developed. Considering the existing management guidelines for these treatment-induced conditions, clinical applicability and standardization of grading methods has remained a cause of concern globally, particularly in Asian countries. In this study, we attempted to collate the literature and clinical experience across Asian countries to compile a practical and implementable set of recommendations for Asian oncologists to manage skin- and mucosa-related toxicities arising from different types of radiation, with or without the addition of cetuximab or chemotherapy. In December 2013, an international panel of experts in the field of head and neck cancer management assembled for an Asia–Pacific head and neck cancer expert panel meeting in China. The compilation of discussion outcomes of this meeting and literature data ultimately led to the development of a set of recommendations for physicians with regards to the approach and management of dermatological conditions arising from RT, chemotherapy/RT and cetuximab/RT, and similarly for the approach and management of mucositis resulting from RT, with or without the addition of chemotherapy or cetuximab. These recommendations helped to adapt guidelines published in the literature or text books into bedside practice, and may also serve as a starting point for developing individual institutional side-effect management protocols with adequate training and education.

Capecitabine-Based Chemoradiotherapy with Adjuvant Capecitabine for Locally Advanced Squamous Carcinoma of the Uterine Cervix: Phase II Results

OBJECTIVES Cisplatin-based chemoradiotherapy is the standard treatment for locally advanced cervical cancer but causes considerable toxicity. Capecitabine and radiotherapy show preclinical synergy and clinical activity. The activity, tolerability, and oral administration of capecitabine make it an attractive adjunctive therapy. METHODS In this phase II study, patients with untreated International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer received capecitabine, 825 mg/m(2) twice daily (Monday-Friday), during radiation (45 Gy per 25 fractions external-beam radiotherapy and 26 Gy high-dose rate brachytherapy to point A, maximum 8 weeks), followed by six cycles of capecitabine, 1,000 mg/m(2) twice daily (days 1-14 every 21 days). RESULTS The overall response rate in 60 patients was 88% (95% confidence interval [CI], 77.4%-95.2%), including complete responses (CRs) in 80% of patients. The 1-year progression-free and overall survival rates were 86% (95% CI, 77%-95%) and 95% (95% CI, 89%-100%), respectively. At 23 months, 76% of patients were progression free (95% CI, 65%-88%) and CR was maintained in 90% (95% CI, 81%-99%) of the 48 patients achieving a CR. There were three grade 3 or 4 treatment-related events: reversible grade 4 hypokalemia, grade 3 diarrhea, and grade 3 hand-foot syndrome. CONCLUSIONS Capecitabine-based chemoradiotherapy with adjuvant capecitabine is a well-tolerated option with an early signal of efficacy meriting further evaluation.

13‐cis‐Retinoic Acid and Interferon‐α2a Therapy in Locally Advanced Squamous Cell Carcinoma of the Cervix: p53 Alteration, Proliferating Cell Nuclear Antigen Expression and Angiogenesis Response*

Objective:To evaluate prognostic importance of p53, PCNA and vasculariza‐tion alteration in patients with locally advanced cervical squamous cell carcinoma (SCC) after combination therapy with 13‐cis‐retinoic acid (13cRA) and interferon‐α2a (IFN‐α2a).