In a previous study, we reported a 72% response rate (CR = 52%) in patients with unresectable head and neck (H&N) carcinomas treated with simultaneous carboplatin (CBDCA) and radiotherapy (RT). Bleomycin (Bleo), a known radio-sensitizing agent, has been shown to increase response rates when given together with RT in similar patients. To explore the nonoverlapping toxicities of these two agents, we combined i.v. CBDCA (100 mg/m2/week), Bleo (5 units on day 1 and 4/weekly) and standard doses of RT in patients with unresectable H&N carcinomas. Chemotherapy (CT) was continued until completion of RT. Twenty-three (13 males, 10 females) previously untreated patients with stage IV squamous cell carcinoma of the H&N were treated at the University of Maryland Medical Center: 61 % had oropharyngeal cancers; 26%, hypopharynx; 9%, oral cavity; and 4%, an unknown primary. Moderate to severe mucositis developed in 90%, which required RT interruptions of up to 3 weeks. After a median follow-up (FU) of 18 months, 35% achieved a complete response (CR) and 65% died from progressive disease. These preliminary data suggest that the addition of Bleo increases mucosal toxicity substantially and, while a moderate response rate was observed, it is unlikely that the CR rate will be higher than CBDCA/RT, which was also better tolerated and hence more suitable to multimodal approaches. Head and neck cancer, advanced
PURPOSE We used population pharmacokinetic-parameter estimates and designed a fixed dosing schedule to maintain plasma suramin concentrations between 100 and 300 micrograms/mL and then evaluated its performance. MATERIALS AND METHODS On day 1, patients received a 200-mg test dose and 1,000-mg/m2 loading dose. On days 2, 3, 4, and 5, patients received 1-hour infusions of 400, 300, 250, and 200 mg/m2, respectively. Subsequent 1-hour infusions of 275 mg/m2 were given on days 8, 11, 15, 19, 22, 29, 36, 43, 50, 57, 67, and 78. Therapy was discontinued for dose-limiting toxicity (DLT) or progressive disease (PD). Patients were to be removed from the fixed dosing schedule if, after day 5, three consecutive peak plasma suramin concentrations were greater than 300 micrograms/mL. RESULTS Forty-two patients, including 40 with hormone-refractory prostate cancer (HRPC), received 700 infusions. Forty patients were assessable for toxicity; 38 were assessable for response. Two patients with preexisting pulmonary disease died early of respiratory insufficiency. Treatment was discontinued in five patients due to DLT and in seven due to PD. No patient had treatment discontinued due to repeated peak plasma suramin concentrations > or = 300 micrograms/mL. The fixed dosing schedule was precise, unbiased, and well tolerated. DLT consisted of grade 4 nephrotoxicity (n = 2), neurotoxicity (n = 2), and corticosteroid-induced psychosis (n = 1). Three patients, who received all 18 doses of suramin per protocol, developed severe, but not dose-limiting, malaise, fatigue, and lethargy. Twenty-four of 36 assessable patients with elevated serum prostate-specific antigen (PSA) levels had a > or = 50% reduction, lasting more than 4 weeks, and 18 had a > or = 75% reduction, lasting more than 4 weeks. Twelve of 23 (52%) symptomatic HRPC patients noted a subjective improvement in pain. There were no measurable responses in four patients with measurable disease. The estimated median survival time in 38 assessable patients with HRPC was 18.8 months. The estimated median time to progression in 35 patients, for whom data were available, was 10.1 months. CONCLUSION This easily implemented schedule allowed suramin to be administered safely as an intermittent bolus injection. Toxicity was manageable and reversible.
e16092 Background: Su is a standard treatment (tx) for mRCC. Octogenarian pts (aged ≥ 80) are often considered to be unfit for su tx, and recommendations for their tx is limited by the paucity of clinical trials data in this population. We aimed to study baseline characteristics and outcome of octogenarian vs young (aged ≤ 45) pts with mRCC treated with su Methods: We performed an international multicenter retrospective study of pts with mRCC, who were treated with su in 8 centers across 2 different countries. We compared baseline characteristics and outcome of octogenarian versus young pts. The effect of very old age on response rate (RR), progression free survival (PFS) and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chi-square test and partial likelihood test from cox model. Furthermore, univariate and multivariate analyses of association between clinicopathologic factors and age, and outcome were performed using the entire pt cohort. Results: Between 2004-2013, 36 octogenarian (group 1; median age 83) and 37 young (group 2; median age 42) mRCC were treated with su. The groups were balanced regarding the following baseline clinicopathologic characteristics: gender, HENG risk, past nephrectomy, mRCC histology, ≥ 2 metastatic sites, lung/liver/bone metastasis, prior targeted tx, smoking status, use of angiotensin system inhibitors (ASIs), pre-tx neutrophil to lymphocyte ratio (NLR) > 3, and sunitinib induced hypertension (HTN). In group 1 vs 2, 53% vs 27% (p = 0.006) had dose reduction/treatment interruption d/t side effects. Clinical benefit (partial response + stable disease) in group 1 vs 2 was 76% vs 84%, while 24% vs 16% had disease progression within the first 3 months of tx (p = 0.09). Median PFS was 11 vs 8 months (p = 0.1). Median OS was 22 vs 20 months (p = 0.7). In multivariate analyses of the entire pt cohort (n = 73), age was not significantly associated with PFS or OS. Conclusions: Su is active in octogenarian mRCC pts. Vs young pts, a significantly higher proportion of octogenarian pts had dose reduction/treatment interruption d/t side effects.
e15597 Background: Several studies have suggested the existence of a “trial effect”, in which for a given treatment, participation in a clinical trial is associated with a better outcome of cancer patients. The VEGFR inhibitor sunitinib is a standard treatment for mRCC. The effect of clinical trial participation on the outcome of sunitinib treatment in mRCC is poorly defined. Aims: To study the effect of clinical trial participation on outcome of mRCC patients treated with sunitinib. Methods: Records from 275 mRCC patients treated with sunitinib from 2004 to 2012 in 7 centers across 2 countries were reviewed. We compared the response rate, progression free survival, and overall survival, between clinical trial participants (n=49) and a matched cohort of non participants (n=49) who who received standard therapy. Each patient participating in a clinical trial was individually matched with a non participant by clinicopathologic factors. Progression free survival and overall survival were determined by Cox regression. Results: The groups were matched by age (median 64), gender (male 67%), Heng risk (favorable 24%, intermediate 60%, poor 16%), ECOG performance status (0-1 92%), prior nephrectomy (92%), renal cell carcinoma histology (clear cell 80%), sunitinib induced hypertension (56%), and sunitinib dose reduction/treatment interruption (41%). In clinical trial participants versus non participants, objective response was partial response/stable disease 80% (n=39) versus 73% (n=36), and progressive disease at first imaging evaluation within the first 3 months (mos) 20% (n=10) versus 27% (n=13) (p=0.63, OR 1.2). Median progression free survival was 10 versus 11 mos (HR=0.96, p=0.84), and median overall survival 23 versus 24 mos (HR=0.97, p=0.89). Conclusions: In mRCC patient treated with sunitinib, the outcome of clinical trial participants was similar to matched non participants who received standard therapy.
