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Abstract
K-ras wild-type carcinoma is a tumour that is sensitive to treatment with anti-cancer and anti-EGFR drugs: the combination of Cetuximab and Panitumumab with chemotherapy (Cetuximab) or as a single therapy (Panitumumab). Case Report: The clinical case presented here refers to a 68-year-old patient who had been diagnosed with adenocarcinoma of the recto sigmoid with pelvic recurrence three years after surgery. The patient had a severe co-morbidity: correlated B-type liver cirrhosis. First-line chemotherapy was begun with Oxaliplatin plus Capecitabine (CAPOXI) following a relapse, and this continued for six months (six cycles), when the treatment was interrupted because of the disease’s progression and hematological and gastrointestinal toxicity. Following an assessment of the K-ras, diagnosed as wild type, the patient was excluded from second-line chemotherapy treatment because of decompensated cirrhosis and the persistence of thrombocytopenia and leukopenia. The patient was put forward for biological treatment with an anti-EGFR monoclonal antibody (Panitumumab). Panitumumab was administered at a dosage of 6 mg/kg every 2 weeks for 17 months; the treatment was well tolerated, despite the cirrhosis, and the main toxicity was the skin rash. Conclusion: In patients with severe comorbidities such as cirrhosis of the liver and K-ras wild-type carcinomas, therapy with a monoclonal antibody such as Panitumumab is a treatment that is well tolerated, with few serious toxic side-effects; it also offers advantages in terms of survival and clinical benefits.
Highlights
Colorectal cancer represents one of the major causes of morbidity and mortality from neoplasias in all western and highly-technologically developed countries
In stage IV the role of medical oncology treatment is of primary importance; chemotherapy with fluorinated pyrimidines (Fluorouracil and Capecitabine) with Oxaliplatin or Irinotecan (FOLFOX, FOLFIRI, or XELIRI or XELOX). [1] [2] are schemes that have resulted in an increase in average survival rates ranging from 6 months to more than 20
Our evaluation on the choice of the best treatment for our patient was made in the wake of these data and given the more important comorbidity: cirrhosis of the liver―we excluded treatment with Irinotecan +/− with 5-FU and Currently the strategy for the treatment of metastatic colorectal carcinoma cannot take into account the evaluation of the mutational status of K-ras ref. [9]-[11], which may be present in two forms: mutated and wild-type
Summary
Colorectal cancer represents one of the major causes of morbidity and mortality from neoplasias in all western and highly-technologically developed countries. The use of anti-EGFR antibodies has demonstrated how it has been possible to achieve limited benefits, in terms of survival, in patients that were resistant to previous lines of chemotherapy including Oxaliplatin and Irinotecan This has been demonstrated for both Cetuximab (hybrid antibody) and Panitumumab (humanized antibody) [3], but appears limited to patients who do not present mutations of the KRAS. In cases where the KRAS is mutated the drug is ineffective [7]; in the presence of mutations in KRAS, which determine the constitutive activation, the proliferative signal is independent from the stimulus EGF In these cases the block EGFR is not able to inhibit cell proliferation, making compartment the therapeutic effect of the antibody. These mutations were found in 40% of cases of cancer of the colon and rectum [8]
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