Anas Al-Janadi

Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma

The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patients risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

Management of locally advanced and metastatic colon cancer in elderly patients.

Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patients functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer.

Randomized phase II trial of docetaxel (Doc) and prednisone (Pred) with or without AZD2171 (cediranib), in chemotherapy-naive, metastatic castrate-resistant prostate cancer (mCRPC) (NCI 7451).

38 Background: Cediranib + Doc were shown in a phase I trial to be feasible, with early evidence for efficacy in mCRPC patients (pts). A multi-center randomized Phase II screening trial of Cediranib+Doc+Pred (Arm A) vs. Doc+Pred (Arm B) was initiated in mCRPC pts. METHODS mCRPC pts with no prior chemotherapy were eligible. All received Doc at 75 mg/m2IV q 3 weeks and Pred 5 mg po bid. Cycle length was 21 days. Arm A pts also received Cediranib at 30 mg po daily. The primary endpoint was 6-month progression-free survival (PFS). We hypothesized 6-month PFS rates of 0.70 on Arm A and 0.50 on Arm B. Secondary endpoints included toxicity, PSA response, and RECIST response. Here we report the toxicity and PSA response data. RESULTS Of 58 pts enrolled, 57 were treated (29 Arm A, 28 Arm B). Median age = 68 years (range 51-84); 33% African-American, 63% Caucasian; median baseline PSA136 ng/mL (range 0.12 - 3,650); 57% had Gleason grade 8-10; and 40% had both bone/ visceral disease. Median nadir PSA was 10.5 ng/mL (range 0.10 - 1,484) in Arm A, and 25.9 ng/mL (range 0.00 - 2,076) in Arm B. Median number of cycles (range): Arm A = 9 (0 - 31); Arm B = 6.5 (1-39 ). 68% pts in Arm A required a dose reduction of at least one Cediranib dose level. Doc dose was reduced in 45% pts on Arm A and in 18% pts on Arm B. Primary grade 4 toxicity was neutropenia (11 [38%] pts A; 5 [18%] pts B), which prompted Cediranib dose reduction. Grade 3 toxicities included fatigue (9 (31%) A, 1 (4%) B); hypertension (8 (28%) A, 1 (4%) B); anemia (6 (21%) A, 2 (7%) B); neutropenia (4 (14%) A; 6 (21%) B); diarrhea (3 (10%) A, 1 (4%) B); deep vein thrombosis (2 (7%) A, 1 (4%) B); and pulmonary embolism (1 (3%) A). An amendment reduced Cediranib to 20 mg daily dose. PSA decrease ≥ 90% at nadir occurred for 13/29 = 45% on Arm A, and 6/28 = 21% on Arm B. PSA decrease ≥ 50% at nadir occurred for 19/29 = 66% on Arm A, and 17/28 = 61% on Arm B. Clinical partial response rates were 8/15 = 53% on Arm A and 3/9 = 33% on Arm B. CONCLUSIONS The addition of Cediranib to Doc/Pred has increased toxicity but may be associated with higher rates of PSA response and clinical response in mCRPC patients. PFS results will be reported. CLINICAL TRIAL INFORMATION NCT00527124.

An overview of the toxicities of checkpoint inhibitors in older patients with cancer

Checkpoint inhibitors offer an exciting new option for treatment of a wide variety of cancers. By binding to surface receptors or their associated ligands on T cells, this class of drugs enhances immune activation and response to cancer cells. In available studies, the drugs are well tolerated, although toxicity involving skin, gastrointestinal tract, liver, lungs, and endocrine organs has been observed. Unfortunately, few studies to date have included patients older than 70 years of age. Since aging has been linked to changes in immune function, there are theoretical concerns that this patient population might experience a different profile of adverse events. This article reviews the tolerability of checkpoint inhibitors in older patients with cancer in clinical practice.

Thyroid Metastases from Squamous Cell Carcinoma of Gallbladder

Gallbladder cancer is a relatively uncommonmalignancy with approximately 5,000 new cases diagnosed each year in the USA [1, 2]. The majority of gallbladder cancers are adenocarcinoma (about 90 %) with squamous cell carcinoma accounting for only about 1–2 % of all cases [3–6]. The overall prognosis of squamous cell carcinoma is significantly worse than adenocarcinoma [5]. Gall bladder cancer is often diagnosed at an advanced stage due to the aggressive biological nature of the tumor and non-specific initial clinical presentation, such as bloating and/or right upper quadrant discomfort. In other instances, gallbladder cancer is found incidentally at surgery or on pathologic review following cholecystectomy [7]. The most common sites of distant metastases are the peritoneum, liver, and lung [8]. However, it is known to metastasize to unusual sites such as skin and subcutaneous tissue, breast, heart, and muscle [9, 10]. Metastasis of adenocarcinoma of the gallbladder to the thyroid has also been reported in the past [11]. Case Report