study of i line folfox + panitumumab vs 5fu + panitumumab in ras and braf wt metastatic colorectal cancer elderly patients

Conditions: Elderly Metastatic Colorectal Cancer Patients

Summary: * few data are available about the treatment of metastatic colorectal cancer (mcrc) elderly patients with anti-egfr agents in combination with chemotherapy. up today, most of the available data are from retrospective/post-hoc analyses, making them difficult to translate to everyday clinical practice. * folfox plus panitumumab is a standard first-line therapy option for ras wild-type untreated mcrc patients. slight adjustments in chemo-dosage are commonly applied in routinary practice to elderly patients, but those modified schedules have never been prospectively tested. * in elderly patients, a reasonable upfront treatment is a fluoropyrimidine-based monotherapy plus bevacizumab, irrespectively of the molecular status of ras. * braf mutation is a strong negative prognostic factor associated to advanced age, poor performance status (ps), extended and aggressive disease and is associated to a lack of benefit from anti-egfr moab. * clinical definition of elderly (over 70 years old) crc patients that may deserve a more or less intensive combination therapy is still debated. the cut-off of 75 years old combined with ecog ps assessment is a reasonable approach for clearly defining candidates to different approaches31. * several geriatric screening tools have been used to identify patients with a geriatric profile potentially predicting for overall survival and risk of toxicity. the g8 screening tool has been validated in cancer patients showing the strongest prognostic value for overall survival; the crash score is able to stratify patients according an estimated risk of treatment-related toxicities. on the basis of these considerations, the investigators designed the present randomized phase ii trial of first-line therapy panitumumab in combination with simplified folfox or with 5-fluorouracil, in previously untreated elderly patients with ras and braf wild-type unresectable mcrc.


Eligibility criteria:
inclusion criteria * written informed consent to study procedures and to molecular analyses. * histologically proven diagnosis of colorectal cancer. * initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease. * at least one measurable lesion according to recist1.1 criteria. * availability of a tumoral sample (primary and/or metastatic sites). * age ≥ 70 years. * ecog ps 1 or 2 for patients aged 70 to 75 years; ecog ps 0 or 1 for patients aged \> 75 years. * life expectancy of at least 12 weeks. * previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse. * ras and braf status wild-type of primary colorectal cancer or related metastasis, centrally assessed. * neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l, hgb ≥ 9 g/dl. * total bilirubin ≤ 1.5 time the upper-normal limits (unl) of the normal values and asat (sgot) and/or alat (sgpt) ≤ 2.5 x unl (or \<5 x unl in case of liver metastases) alkaline phosphatase ≤ 2.5 x unl (or \<5 x unl in case of liver metastases). * creatinine clearance ≥ 50 ml/min or serum creatinine ≤1.5 x unl. * male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception). * geriatric assessment by means of g8 screening tool and crash score. * will and ability to comply with the protocol. exclusion criteria * previous treatment for metastatic disease. * radiotherapy to any site within 4 weeks before the study. * previous adjuvant oxaliplatin-containing chemotherapy. * previous treatment with egfr inhibitors. * untreated brain metastases or spinal cord compression or primary brain tumors. * history or evidence upon physical examination of cns disease unless adequately treated. * symptomatic peripheral neuropathy \> 1 grade ncic-ctg criteria. * creatinine clearance \ 1.5 x unl. * clinical signs of malnutrition. * neutrophils \<1.5 x 109/l, platelets \<100 x 109/l, hgb \<9 g/dl. * diagnosis of interstitial pneumonitis or pulmonary fibrosis. * active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration. * clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, new york heart association (nyha) grade ii or greater congestive heart failure (chf), serious cardiac arrhythmia requiring medication. * treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer) * other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ. * lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication. * definite contraindications for the use of corticosteroids and antihistamines as premedication. * known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs. * any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies. * sexually active males unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.