Hussein Soudy

A modern regimen of pre-operative concurrent chemo-radiation therapy in locally advanced rectal cancer

To evaluate the efficacy and toxicity of preoperative concurrent capecitabine and radiotherapy in the treatment of resectable locally advanced rectal cancer (LARC).

Co-administration of intravesical bacillus Calmette-Guérin and interferon α-2B as first line in treating superficial transitional cell carcinoma of the urinary bladder.

Study Type – Therapy (individual cohort)

Whole body 18F-FDG PET predicts progression free and overall survival in squamous cell carcinoma of the esophagus: results of a prospective trial

BACKGROUND AND OBJECTIVES 18F-FDG PET yields physiologic information that allows for identifying cancer based on altered tissue metabolism. The aim of this study was to prospectively validate the predictive value of positron emission tomography (PET) in squamous cell carcinoma (SCC) of the esophagus treated by pre-operative chemotherapy followed by esophagectomy. DESIGN AND SETTING Prospective efficacy and toxicity study of patients enrolled between January 1999 and September 2003. PATIENTS AND METHODS Twenty-one patients with SCC of the esophagus who were potentially resectable underwent 18F-FDG PET imaging before the first cycle of neoadjuvant chemotherapy and at least 14 days after the third cycle. A patient was classified as a metabolic responder when the metabolic activity of the primary tumor as measured by the maximum standardized uptake values had decreased by 50% or more at the time of the second 18F-FDG PET. RESULTS The median age of the study cohort was 60 years with a range of 39-70 years; 12 patients were males and 9 were females. 18F-FDG PET had increased activity in the primary tumor in all patients. Metabolic response occurred in 14/21 patients (66%), while 7/21 (33%) patients did not show a metabolic response. Metabolic responders had a high clinical response rate (92%), a median progression free survival (PFS) of 16.4 months and a median overall survival (OS) of 35.3 months. In contrast, prognosis was poor for metabolic non-responders with a clinical response rate of 42% (P=.025), a median PFS of 7.13 months (P=.032) and median OS of 12 months (P=.038). CONCLUSION Our results demonstrate that changes in tumor metabolic activity after neoadjuvant chemotherapy predicts PFS and OS in esophageal SCC patients.

Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5‐fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5‐fluorouracil/leucovorin. We evaluated a triple‐chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m2. Median follow‐up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression‐free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K‐ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3‐weekly triple‐chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first‐line treatment of mCRC, although at the expense of a high level of toxicity.

Phase II Trial of Neoadjuvant Cisplatin, 5-Fluorouracil and Interferon-Alpha in Operable Squamous Cell Carcinoma of the Esophagus

Background: The combination of 5-fluorouracil (5-FU), cisplatin and interferon (IFN)-α was found to result in a high response rate in advanced esophageal squamous cell carcinoma (SCC). Methods: Resectable cases of esophageal SCC were treated with 3 cycles of chemotherapy consisting of cisplatin 70 mg/m2 i.v. on day 1, 5-FU 500 mg/m2/day i.v. as a continuous infusion on days 1–5 and IFN-α 4 million units/m2/day s.c. on days 1–5. Cycles were repeated every 21 days. Esophagectomy was performed 3–5 weeks after the 3rd cycle of chemotherapy. Results: Thirty patients were enrolled in the trial. Toxic death was observed in 1 patient because of esophageal perforation. Pathologically, complete response was observed in 4 of 23 patients who had esophagectomy. At a median follow-up period of 21.4 months, median progression-free survival was 11.5 months and median overall survival was 26.3 months. Conclusion: This regimen has substantial activity in localized SCC of the esophagus with encouraging survival duration.

Saudi Oncology Society clinical management guidelines for renal cell carcinoma.

In this report, guidelines for the evaluation, medical and surgical management of renal cell carcinoma is presented. It is categorized according to the stage of the disease using the tumor node metastasis staging system, 7th edition. The recommendations are presented with supporting evidence level.

Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by definitive surgery in patients with operable rectal cancer

BACKGROUND Achieving a high rate of complete pathological response with pre-operative chemoradiotherapy in rectal cancer is an unmet need. We evaluated the efficacy and toxicity of the combination of cetuximab, capecitabine and radiation therapy in the pre-operative setting of localized rectal cancer. PATIENTS AND METHODS Patients with clinically staged T3, T4 or nodepositive rectal cancer were treated with concurrent capecitabine and radiotherapy with weekly cetuximab starting one week before the start of radiation. This was followed by total mesorectal excision within 6-8 weeks. All patients achieving R0 resection received adjuvant capecitabine for 6 cycles. RESULTS Fifteen patients were treated and all underwent surgery. Sphincter preservation was achieved in 11 patients (73.3%) and pathological complete response in two. With a median follow up of 48 months (range 8.4-57.5), 12 patients were relapse-free and 14 were alive with 4-year relapse free survival of 80%. Overall survival was 93%. Significant grade 3 and 4 toxicity was mainly cetuximab-induced skin reactions (33%), radiation-induced skin toxicity (13%) and diarrhea (20%). CONCLUSIONS Adding cetuximab to pre-operative concurrent capecitabine and radiotherapy provides modest efficacy with manageable toxicity.

Combination chemotherapy with capecitabine (C), irinotecan (I), oxaliplatin (O), and bevacizumab (B; XELOXIRIA) as first-line treatment of metastatic colorectal cancer (MCRC): Preliminary results of a phase I-II trial.

e14073 Background: FOLFOXIRI demonstrated tolerable toxicities and improved efficacy compared to FOLFIRI in MCRC in a phase III trial. Oral C has demonstrated similar efficacy to IV 5-FU and might substitute IV 5-FU in the FOLFOXIRI regimen. METHODS This is phase I-II prospective trial using fixed dosed of capecitabine (C), oxaliplatin (O), and bevacizumab (B) in combination of escalating doses of Irinotecan (I) in metastatic and locally advanced unresectable CRC patients (pts). The objectives of the study were to define the recommended dose (RD) of I in combination with C, O and B, safety and efficacy of the combination. The planned treatment in the first 3 pts was: I 150 mg/sqm over 90 min on day 1, O 130 mg/sqm over 2-h on day 1, C 2,000 mg/sqm/day from day 1 to 14, and Bevacizumab 7.5 mg/kg over 30 min on day 1. Cycles repeated every 3 weeks. I dose was increased to 200 mg/sqm or C dose was decrease to 1,300 mg/sqm/day in subsequent groups of 3 pts on the basis of the observed dose limiting toxicities (DLT). RESULTS Until today, 29 pts have been enrolled. We report here the results on the first 20 pts. Pts characteristic are: sex (M/F) = 12/8, PS (0/1/2) = 2/14/4, age (median/range) = 52/24-73 years, sites of disease (single/multiple) = 6/14. The DLT was G3-4 diarrhea that was observed in 2 out of 3 pts receiving I at 200 mg/sqm, The I recommended dose was 150 mg/sqm which continued as phase II trial. Grade 3-4 toxicities were: nausea and vomiting 26%, diarrhea 52%, neutropenia 16%, thrombocytopenia 5.3%, fatigue 21%. Response evaluation was done according to ITT analysis. 5 Pts were not assessable for response because of 2 or less cycles of chemotherapy (3 consent withdrawal, 2 grade 4 toxicity). One CR, and 8 PR were observed for an overall response rate of 45% (95%CI: 34-56%). Two had SD and 3 progressed. At a median follow-up of 10 months median PFS is 18.3 months and median OS was not reached. CONCLUSIONS XELOXIRIA is toxic with diarrhea being the DLT. The recommended dose of I is 150 mg/sqm. Recruitment will continue with reduction in the C dose to 1,600 mg/sqm daily. Short follow up prohibits meaningful interpretation of efficacy.