Oxaliplatin

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

Get Instant Access

Oxaliplatin is a third generation platinum with a 1,2 diaminocyclohexane carrier ligand that forms DNA adducts and secondary strand breaks. It has a distinctive neurotoxicity profile, which includes an acute cold-induced sensory neuropathy characterized by dysesthesias and paresthesias during or soon after the infusion and a delayed onset dose-dependent neuropathy occurring hours to days after treatment. The latter typically occurs in 10 to 15% of patients after a cumulative dose of 780 to 850 mg/m2, with at least partial reversibility in 75% of patients within 3 to 5 months of treatment discontinuation. In a randomized trial comparing infusional 5-FU/LV (LV5FU2), single-agent oxaliplatin and the combination (FOLFOX) in 459 patients with recurrence following IFL, treatment with FOLFOX yielded higher response rates (9.9% vs 1.3% oxaliplatin vs 0% LV5FU2) and a longer time to progression (4.6 months vs 1.6 months vs 2.7 months) (Rothenberg et al, 2003). A survival advantage for first line FOLFOX has been established in a three-arm NCCTG-led intergroup trial (N9741) of

TABLE 97-1. Phase III Trials of Irinotecan Combined with 5-Fluorouracil and Leucovorin

Study

0038[31]

0038[31]

5-FU/LV Bolus

Irinotecan + Bolus 5-FU/LV*

5-FU/LV Infusional

Irinotecan + Infusional 5-FU/LV

Number of patients

221

222

188

199

Response rate

21%

39% (p < .001)

22%

35% (p < .005)

Median TTPf

4.3 mo

7.0 mo (p =.004)

4.4 mo

6.7 mo (p < .001)

Grade 3 or greater* toxicity

-

-

-

-

Diarrhea

13%

23%

6%

14%

Vomiting

4%

10%

2%

4%

Febrile neutropenia

15%

7%

1%

3%

Neutropenia

67%

54%

14%

46%

*IFL (irinotecan and bolus 5-tluorouracil/leucovorin). fTlme to progression.

^National Cancer Institute Common Toxicity Criteria.

*IFL (irinotecan and bolus 5-tluorouracil/leucovorin). fTlme to progression.

^National Cancer Institute Common Toxicity Criteria.

patients with advanced CRC randomly assigned to bolus IFL, FOLFOX, or a combination of irinotecan plus oxali-platin (IROX) (Goldberg et al, 2004).As presented in Table 97-2, FOLFOX was associated with improved response rates, a longer time to progression and a longer median survival when compared to IFL and IROX.

In an analysis of randomized trials, a linear association between a prolonged median survival and the successive availability of 5-FU, irinotecan and oxaliplatin was seen with median survivals approaching a previously unheard of 21.4 months, hence emphasizing the need for access to all three active agents in order to significantly impact the survival of patients with advanced CRC (Grothey et al, 2004). In addition, based on case series and phase II data, there now exists the hope of altering the natural history for selected patients with unresectable disease by downstaging liver-limited metastases with primary chemotherapy and rendering them amenable to a potentially curative resection (Giacchetti et al, 1999; Alberts et al, 2003).

Given the number of options currently available, patients with advanced CRC warrant an early referral to medical oncology for discussion. At present, either oxali-platin or irinotecan in combination with 5-FU/LV (preferably as an infusional regimen) represent reasonable strategies for first line primary chemotherapy in good performance status patients with unresectable metastatic CRC. The choice of regimen can be somewhat tailored by the differences in toxicity profiles for oxaliplatin and irinotecan. Capecitabine may be offered to patients not suitable for combination therapy.

Was this article helpful?

0 0
Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

Get My Free Ebook


Post a comment