الفهرس 
Epidemiology and Risk FactorsOnly 14 pages are availabe for public view
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Abstract
This prospective phase II study was conducted to assess the efficacy and safety of the use of maintenance low dose capecitabine, after best response achieved with previous standard chemotherapy in colorectal cancer patients with irresectable metastasis. The study was conducted in Clinical Oncology and Nuclear medicine department Ain Shams University Hospitals during the period from June 2009 to December 2011.
All 40 eligible patients fulfilling the inclusion criteria and, after pretreatment assessments,received capecitabine at a dose of 500 mg/m2 (with a maximum of 1000 mg total dose) twice daily 5 days/week. Patients with a stable disease were considered responders, and maintenance of the tumor response was evaluated every 3 cycles or earlier in case of presence of symptoms or signs of progression.
The median duration of treatment was 34 weeks with standard of error of 4.096 weeks (ranging from 4 to 86 weeks). The mean number of cycles received was 7.5 cycles, ranging from 1 to 21.5 cycles. The median follow up interval was 12 months, ranging from 1 to 30 months.
The study regimen proved to be quite tolerable with no grade 4 toxicities detected during the use of low dose capecitabine. Grade III was detected in only 3 patients who developed grade III hand foot syndrome, however, toxicity was the cause of study termination in only 2 of them while the third improved after treatment delay and 25% dose reduction.
Non-hematological toxicities were as follows: Hand foot syndrome (60%), fatigue (50%), anorexia (32.5%), abdominal pain (31.5%), diarrhea (22.5%), hyperbilirubinemia (17.5%), mucositis (17.5%), nausea (5%), vomiting (5%).
Hematological toxicities were as follows: neutropenia (17.5%), anemia (12.5%), and thrombocytopenia (5%).
Out of 40 patients recruited in this study, 35 patients (87.5%) developed disease progression, while study termination was due to toxicity in 2 patients (5%), and for unrelated medical or surgical conditions in 3 patients (7.5%).
The estimate mean progression free survival was 37 weeks. The median time to progression was 34 weeks with standard of error of 4.096 weeks (ranging from 4 to 86 weeks).
Different clinico-pathological parameters were defined to compare values of PFS and OS between cases included in the study, which are: age, gender, performance status, primary site, time to metastases (synchronous vsmetachronous metastases), number of metastatic sites, previous surgery, radiotherapy, number of previous chemotherapy lines, and response to previous chemotherapy.
Progression free survival was significant between males and females [P value= 0.021], mostly related to greater number of females recruited in the study.
Progression free survival was highly significant between patients of different performance status. Mean progression free survival for patients of grade 0 ECOG PS was 56.736 weeks (95% confidence interval 38.600 to 74.873 weeks), patients of grade 1 was 27.662 weeks (95% confidence interval 21.312 to 34.012 weeks), and patients of grade 2 was 17.333 weeks (95% confidence interval 0 to 34.823 weeks) [P value= 0.019].
Progression free survival was also significant regarding time to metastases. Mean progression free survival for synchronous metastases was 30.072 weeks (95% CI21.740 to 38.404 weeks), while the mean progression free survival for metachronous metastases was 49.000 weeks (95% CI30.178 to 67.822 weeks) [P value=0 .048].
Progression free survival was significant regarding the response to previous chemotherapy. Mean progression free survival for patients who had achieved CR or PR was 53.688 weeks (95% CI33.489 to 73.886 weeks), while the mean progression free survival for patients who had achieved SD was 31.427 weeks (95% CI21.839 to 41.015 weeks) [P value= 0.05].
Progression free survival was not significant between patients≤ 50 years of age or those above 50, colon versus rectum as a primary site, number of metastatic sites, or previous surgery, or number of previous chemotherapy lines received.
The 1 and 2 years survival probabilities were 65.2% and 59.8%, respectively, with significant difference between patients with different performance status (P value= 0.021), and response achieved with previous chemotherapy (P value= 0.021).
After study termination, 23 patients (57.5%) received standard palliative chemotherapy for metastatic disease, 1 patient (2.5%) received palliative chemoradiation (for recurrent rectal mass), 1 patient (2.5%) underwent palliative surgery (for recurrent colonic mass), while 15 patients (37.5%) have undergone no further management (best supportive care).
To summarize, synchronous metastasis has a significant negative impact on PFS in comparison to metachronous metastases. Better performance status and better objective response to previous chemotherapy have significant positive impact on both PFS and OS. Number of previous chemotherapy lines among the study patients was associated with better survival; however this survival advantage did not reach statistical significance.