Oxaliplatin Irinotecan

Every-3-weeks irinotecan Oxaliplatin plus fluorouradl plus leucovorin Irinotecan 350 mg/m2 IV every 3 weeks Neutropenia, diarrhea (less-than-weekly irinotecan)... 

Carcinoma of colon Fluorouracil plus leucovorin plus irinotecan Oxaliplatin... 

Investigational Approaches. Despite the significant reduction in cancer recurrence and increased survival afforded with fluorouracil-based adjuvant chemotherapy, the results obtained thus far indicate need for continued improvement. Several strategies are underway, including protracted fluorouracil infusion, oral fluorinated pyrimidines, irinotecan, oxaliplatin, and immunotherapy-based therapies. ... 

Given the significant improvements with systemic chemotherapy for metastatic disease achieved with systemic chemotherapy over the past several years, attention has been directed to HAI with non-fluoropyrimidines, including irinotecan, oxaliplatin, and biologic... 

Triple -drug therapy consisting of 5-fluorouracil and leucovorin with oxaliplatin or irinotecan improves survival compared with 5-fluorouracil plus leucovorin alone and is... 

The dose of capecitabine begins at 1250 mg/m2 twice a day when used by itself lower doses are used often when it is given in combination with irinotecan or oxaliplatin or in patients with renal insufficiency. The dose should be taken on a full stomach with breakfast and dinner. Capecitabine administered with warfarin can result in significant increases in the patient s INR and requires close monitoring to prevent bleeding. The convenience of oral administration and an improvement in toxicity make capecitabine a useful alternative to IV 5-FU both by itself and incorporated into other regimens used in colon cancer. 

Goldberg RM, Sargent DJ, Morton RF, et al. A randomized, controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004 22 23-30. 

Either irinotecan or oxaliplatin plus 5-FU and leucovorin is recommended as first-line therapy for MCRC. These regimens result in... 

The most important factor in patient survival is not the initial chemotherapy regimen but ensuring that patients receive all three active drugs (5-FU, irinotecan, and oxaliplatin) at some point in their treatment course. 

Cetuximab, either alone or in combination with irinotecan, can be used in patients with disease progression on irinotecan. Cetuximab monotherapy can also be considered as salvage therapy in patients with oxaliplatin-refractory disease. 

Panitumumab is approved for use in MCRC that no longer responds to previous therapy with 5-FU, irinotecan, or oxaliplatin. 

Patients should be closely monitored for side effects that require aggressive intervention such as irinotecan-induced diarrhea and bevacizumab-induced GI perforation. Patients should be evaluated for other treatment-specific side effects such as oxaliplatin-induced neuropathy, cetuximab and panitumumab-induced skin rash, and bevacizumab-induced hypertension and proteinuria. 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

For patients who cannot tolerate the intensity of the oxaliplatin and irinotecan regimens the standard Mayo (see Poon et al., 1989), Roswell and de Gra-mont Park 5-FU regimens (see de Gramont et al., 1997) remain appropriate. In addition the oral fluo-ropyrimidine pro-drug, capecitabine, is equally beneficial. 

Cetuximab has modest activity in relapsed colorectal cancer as a single agent but is more effective with irinotecan and possibly oxaliplatin based regimens where a doubling of the response rate has been observed. There is some evidence that cetuximab may reverse irinotecan resistance. Toxic effects of cetuximab include hypersensitivity reactions, malaise, nausea, headache and an acneiform rash. 

This benefit comes at a cost of significant toxicity, particularly neuropathic, and more mature data are necessary to demonstrate the ultimate benefit of adjuvant therapies on improved overall survival. So far irinotecan plus 5-FU based therapy has produced disappointing results in adjuvant treatment. Despite the present lack of data addressing overall survival benefit, oxaliplatin plus 5-FU/leucovorin is widely recommended as the gold standard adjuvant therapy for stage 3 disease. For those whose medical fitness or other contra-indications preclude oxaliplatin based therapy 5-FU/leucovorin on a weekly or monthly schedule is recommended. Oral capecitabine for 6 months has recently been reported to be at least equivalent to 5-FU/leucovorin. 

Colorectal cancer (CRC) is the third most common cause of cancer-related death in women and men in the United States. The current therapeutic options for patients with metastatic CRC (mCRC) are 5-fluorouracil (5-FU) based chemotherapy regimens with the addition of irinotecan (CPT-11) or oxaliplatin. It still remains a challenge for oncologists to evaluate the reasons for a wide variation in response and toxicity among patients undergoing systemic 5-FU based chemotherapy. Pharmacogenomics... 

From Ref. (85). Abbreviations 5-FU/LV (5-fluorouracil plus leucovorin) CapeOx (capecitabine plus oxaliplatin) FOLFIRI (infusional 5-FU/LV plus irinotecan) FOLFOX (infusional 5-FU/LV plus oxaliplatin). 

Reconstitution of full-length BRCAl into mouse embryonic fibroblast cells with a disrupted BRCAl led to an increase in resistance to several DNA damaging agents, including the platinum compounds carboplatin and oxaliplatin, the topoisomerase 1 drugs irinotecan and topotecan, and the topoisomerase 11 drugs doxorubicin and etoposide (61). 

FOLFIRI Fluorouracil, leucovorin, irinotecan FOLFOX Fluorouracil, leucovorin, oxaliplatin MP Melphalan, prednisone... 

Oxaliplatin is a third generation diaminocyclohexane platinum analog. Its mechanism of action is identical to that of cisplatin and carboplatin. However, it is not cross-resistant to cancer cells that are resistant to cisplatin or carboplatin on the basis of mismatch repair defects. This agent was recently approved for use as second-line therapy in metastatic colorectal cancer following treatment with the combination of fluorouracil-leucovorin and irinotecan, and it is now widely used as first-line therapy of this disease as well. Neurotoxicity is dose-limiting and characterized by a peripheral sensory neuropathy, often triggered or worsened upon exposure to cold. While this neurotoxicity is cumulative, it tends to be reversible—in contrast to cisplatin-induced neurotoxicity. 

The clinical tumor spectrum for oxaliplatin is not yet fully characterized, but oxaliplatin is considered to be the most effective agent beside 5-fluorouracil (5-FU) and irinotecan against colorectal cancer. It also shows a promising activity in breast cancer, which is only marginally sensitive to the conventional Pt compounds. Oxa-... 

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