Yr Disease-free Survival Research Articles

Phase II trial of concurrent split course hyperfractionated radiotherapy (Hfx RT), cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): Results of RTOG 9911

5509 Background: Recurrent SCCHN, if not curable by surgery or RT, is almost always fatal. Chemotherapy (CTx) alone (eg. DDP, 5FU) yields median survival times (MST) of 8–10 mos and 1 yr survival (OS) of ≤ 35% at best. For limited relapse or patients (pts) with new unresectable SCCHN within previous RT portals, a potential role for re-irradiation combined with radiosensitizing CTx, exists. In a prior phase I trial of HFx RT/ DDP/ P, we observed ≥ 2 yr disease-free survival in 5 of 31 pts (ASCO 1999, A-1551), and therefore exported this regimen to RTOG for broader assessment. Methods: Eligibility stipulated recurrent SCCHN or second 1° tumors (SPT) in a previous RT field; measurable tumor; ≥ 75% of tumor volume previously treated to 45 Gy-75 Gy; ≥ 6 mos elapsed from prior RT, ECOG PS 0–1; ANC ≥1500, plts ≥ 100K, bili ≤1.5 mg/dl, creat ≤ 1.5 mg/dl, and absence of distant mets. Pts received HFx RT (1.5 Gy/Fx BID x 5d every 2 wks x 4), in combination with DDP 15 mg/m2 IV QD x 5 and P 20 mg/m2 IV QD x 5 q 2 wk...

Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and hydroxyurea for patients with advanced and/or recurrent head and neck cancer: Toxicity and outcome results

5561 Background: At University of Chicago, concomitant chemoRT for advanced and recurrent head and neck cancer has been studied for 2 decades. We investigated the addition of CPT-11 as a promising new agent to our established regimen of 5-FU, hydroxyurea (HU), and hyperfractionated RT (HF2X). The goal was to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this regimen. Time to progression, patterns of failure, and survival were secondary endpoints. Methods: Between 8/98 and 8/01, 31 pts with advanced and recurrent H&N cancer were enrolled. Previously untreated pts were eligible if unressectable or had an expected 2 year survival <20%. Pts with metastatic disease were included if local radiotherapy to the H&N was required. 19 previously radiated pts were included. The median prior RT dose was 66.4 Gy (range: 45–88.4 Gy). The starting dose of CPT-11 was 5 mg/m2/d delivered with continuous infusion 5-FU (600 mg/m2/d), HU (500 mg PO q 12 hours) and BID RT (1.5 Gy/fraction). All pts were treated on a 14 d cycle with 5 consecutive days of therapy and a 9 day break. Subsequent cohorts had CPT-11 escalated by 5 mg/m2/d. Subsequently, 14 pts were treated at the MTD. Results: CPT-11 was well tolerated at the 5 mg/m2/d and 10 mg/m2/d dose levels. 3/3 pts treated at the 15 mg/m2/d level, experienced neutropenic DLT during cycles 1–2. 8/18 (44%) evaluable pts had a response; 5 (28%) had a CR, 3 (17%) had a PR, 5 had stable disease (28%) and 5 pts progressed. At a median f/u of 24 mos for surviving pts, (range, 16.5–51), 4 pts (13%) are alive and NED. 2 yr overall survival (OS) and disease free survival (DFS) was 31.3% and 24.4%. Re-irradiated pts had a median survival of 9.5 mos (range: 0.7–50.5) and a 2 yr OS of 24.5%. 2 yr DFS of squamous histology re-irradiation pts was 23%. Conclusions: The MTD and recommended phase II dose of CPT-11/ HF2X was 10 mg/m2/d. Neutropenia was dose limiting. Response rates were reasonable. Further investigation of this regimen may be worth additional study. Re-irradiation with concurrent chemotherapy resulted in the survival of a significant fraction of pts. No significant financial relationships to disclose.

Rapid growth rate: A method of identifying node-negative breast cancer patients with a high risk of recurrence

Among node-negative patients with localized breast cancer (TNM stages T 1–3N 0–1M 0), the rate of disease progression, classified with a clinical method of assessment, was rapid in 12%. Prognosis was substantially worse in the rapid groups than in patients classified as slow or intermediate. For instance, the 10 yr disease free survival rate was 55 and 50% in the rapid groups compared with 71% in the intermediate and 82% in the slow groups. Additionally, among those who did develop recurrent disease, the disease-free interval was shortest in the most rapid group (10 months) and longest in the slow group (50 months). The distinctive prognostic gradients formed by the growth-rate strata persisted when differences in symptomatic state, histologic type, tumor size, menstrual status, age, and treatment were taken into account through the Cox proportional hazards model. The node-negative patients who were identified as rapid have had a high risk of recurrence, while those with slow growth rates had an excellent prognosis. The index could improve therapeutic efficacy in this subset of patients by identifying high risk patients in whom adjuvant therapies may do more good than harm.