The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer. FLOX can be recommended as an effective option in clinical practice.

A B S T R A C T PurposeAlthough chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients and MethodsPatients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). ResultsFrom August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P ϭ .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P ϭ .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. ConclusionPreoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

A B S T R A C T PurposeThe National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial demonstrated that the addition of oxaliplatin to fluorouracil plus leucovorin (FULV) improved disease-free survival (DFS) in patients with stage II or III colon cancer. This analysis is the first publication of overall survival (OS) for the NSABP C-07 study. We updated DFS and examined both end points in clinically relevant patient subsets. Patients and MethodsOther studies have identified patients age 70 or older and those with stage II disease as patient subsets in which oxaliplatin may not be effective. We investigated toxicity as a driver of divergent outcomes in these subsets. ResultsIn all, 2,409 eligible patients with follow-up were randomly assigned to either FULV (FU 500 mg/m 2 by intravenous [IV] bolus weekly for 6 weeks; leucovorin 500 mg/m 2 IV weekly for 6 weeks of each 8-week cycle for three cycles) or FLOX (FULV plus oxaliplatin 85 mg/m 2 IV on days 1, 15, and 29 of each cycle). With 8 years median follow-up, OS was similar between treatment groups (hazard ratio [HR], 0.88; 95% CI, 0.75 to 1.02; P ϭ .08). FLOX remained superior for DFS (HR, 0.82; 95% CI, 0.72 to 0.93; P ϭ .002). The effect of oxaliplatin on OS did not differ by stage of disease (interaction P ϭ .38 for OS; interaction P ϭ 0.37 for DFS) but did vary by age for OS (younger than age 70 v 70ϩ interaction P ϭ .039). There was a similar trend for DFS (interaction P ϭ .073). Oxaliplatin significantly improved OS in patients younger than age 70 (HR, 0.80; 95% CI, 0.68 to 0.95; P ϭ .013), but no positive effect was evident in older patients. ConclusionOverall, the addition of oxaliplatin to FULV has not been proven to extend OS in this trial, but the DFS effect remained strong. Unplanned subset analyses suggest a significant OS effect of oxaliplatin in patients younger than age 70.

Bevacizumab for 1 year with mFOLFOX6 does not significantly prolong DFS in stages II and III colon cancer. However, a significant but transient effect during bevacizumab exposure was observed in the experimental arm. We postulate that this observation reflects a biologic effect during bevacizumab exposure. Given the lack of improvement in DFS, the use of bevacizumab cannot be recommended for use in the adjuvant treatment of patients with colon cancer.

Purpose The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m2, 5 days per week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5 weeks) or oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m2 once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

Acute chest syndrome (ACS) is an important cause of morbidity and mortality in sickle cell disease (SCD). Previous studies reported conflicting pictures of ACS making therapeutic interventions difficult. The Cooperative Study of Sickle Cell Disease prospectively followed 3,751 patients enrolled from birth to 66 years of age for ACS. Data on presenting signs and symptoms, laboratory findings, and hospital course were collected. There were 1,722 ACS episodes in 939 patients. Young children (age 2 to 4 years) presented with fever and cough, a negative physical exam, and rarely had pain. Adults were often afebrile and complained of shortness of breath, chills, and severe pain. Upper lobe disease was more common in children; multilobe and lower lobe disease affected adults more often. Severe hypoxia occurred in 18% of adults tested and could not be predicted by examination or laboratory findings. Bacteremia was documented in 3.5% of episodes, but was strongly influenced by age (14% of infants and 1.8% of patients <10 years). ACS was most common in winter with children having the most striking increase. Transfusion was used less frequently, but earlier in children. Young children were hospitalized for 5.4 days versus 9 days for adults. Fifty percent of adults had a pain event in the 2 weeks preceding ACS and children were more likely to have febrile events. The death rate was four times higher in adults than in children. Fatal cases generally developed rapid pulmonary failure and one third were associated with bacteremia. Age has a striking effect on the clinical picture of ACS. In children, ACS was milder and more likely due to infection, whereas in adults ACS was severe, associated with pain and had a higher mortality rate.

Among colon cancer patients, a BMI greater than 35.0 kg/m2 at diagnosis was associated with an increased risk for recurrence of and death from colon cancer. Further studies are needed to determine pathways between obesity and recurrence risk and whether weight reduction or related interventions would improve prognosis.

Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.