Oxaliplatin

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

Get Instant Access

Oxaliplatin is a novel diaminocyclohexane platinum analogue that acts mainly by causing interstrand and intrastrand cross-links in DNA. Alone or combined with FU and LV, it has shown promising activity in previously treated and untreated patients with metastatic colorectal cancer and in patients with FU refractory disease.

Three phase III prospective randomised trials compared the efficacy of the combination OXA-FU-LV to FU-LV.

The first study compared FOLFOX regimen (oxaliplatin 85 mg/m2 as a 2-hour infusion on day 1 and 2hour infusion of LV 200 mg/m2/day followed by a FU bolus 400 mg/m2/day and 22-hour infusion 600 mg/m2/day for 2 consecutive days every 2 weeks) to the same regimen of infusional FU-LV alone in previously untreated patients with advanced colorectal cancer. Patients treated with FOLFOX4 had a significantly longer progression-free survival (9.0 vs. 6.2 months, p=0.0003) and response rate (50.7% vs. 22.3%, p=0.0001), but no improvement in overall survival (16.2 vs. 14.7 months, p=0.12). Grade 3 and 4 toxicity (neutropenia, diarrhoea and neuropathy) were more common in the oxaliplatin arm but this did not result in impairment of QoL. Survival without disease progression or deterioration in global health status was longer in patients allocated to oxali-platin treatment (p=0.004) [18].

Similar results were observed in a second randomised trial using a chronomodulated schedule. Sixteen percent of the patients receiving FU-LV had an objective response, compared with 53% of those receiving additional oxaliplatin (p<0.001). The median progression-free survival time was 6.1 months with FU-LV and 8.7 months with oxalipaltin and FU-LV (p=0.048). Median survival times were 19.9 and 19.4 months, respectively [19].

A third phase III study randomised between FU bolus 425 mg/m2, LV 20 mg/m2, on days 1-5, repeated every 4 weeks; and oxaliplatin 50 mg/m2, 2-h infusion, FU 2000 mg/m2,24-h infusion, LV 500 mg/m2 on days 1,8,15,22, repeated every 5 weeks (FUFOX regimen). Response rate was more than doubled in FUFOX with 48.3% vs. 22.6% (p<0.0001) and 8.8% of complete response in FUFOX. After a median follow-up of 27.3 months, progression-free survival is signif

Table 3. Phase III randomised trials of oxaliplatin in patients with metastatic colorectal cancer

Author

Trial

Response rate

Progression-free survival

Median survival

(%)

(months)

(months)

De Gramont et al. [18]

FOLFOX

50.7 pS

9 pS

16.2

FU-LV

22.3

6.2

14.7

Giacchetti et al. [19]

FU-LV+OXA chrono

53 pS

8.7 pS

19.9

FU-LV

16

6.1

19.4

Grothey et al. [20]

FUFOX

48.3 pS

7.9 pS

20.4

FU-LV

22.6

5.3

16.1

pS, p value statistically significant pS, p value statistically significant icantly longer in the oxaliplatin arm: 7.9 vs. 5.3 months (p<0.0001). Median overall survival is 20.4 and 16.1 months respectively [20] (Table 3).

Two North American randomised phase III trials have evaluated a second chemotherapeutic line with a regimen containing oxaliplatin in patients with progressive metastatic colorectal cancer after frontline treatment with CPT-11, bolus FU-LV. In the first FOLFOX was found to be superior in response rate (9.6%) to oxaliplatin (1.1%) and FU-LV (0.7%) alone. Mature data from this study, however, failed to show a statistically significant improvement in median survival. Toxic effects, particularly neutropenia and neuropathy, were higher in the FOLFOX arm but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate [21].

In the second, FU-LV with or without oxaliplatin was evaluated in patients with metastatic colorectal cancer after disease progression on sequential fluo-ropyrimidine and CPT-11. FOLFOX was found to be superior to FU-LV in terms of: response rates (13% vs. 2%, p=0.0027), median time to disease progression (4.8 vs. 2.4 months, p<0.0001) and median survival (11.4 vs. 9.9 months, p=0.20). Symptomatic improvement was significantly better for FOLFOX (32% vs. 18%, p=0.05) [22].

The next generation of studies compared CPT-11-based to oxaliplatin-based chemotherapy in patients with newly diagnosed advanced colorectal cancer.

GERCOR group compared FOLFOX with FOLFIRI in patients with advanced colorectal cancer. In this study, patients were crossed over from 1 regimen to the other at the time of progression. These 2 first-line treatments for metastatic and advanced colorectal cancer have demonstrated similar response rates and acceptable toxic effects profiles with no differences in median time-to-first progression (8 vs. 8.5 months) or overall survival (20.6 vs. 21.5 months) for FOLFOX followed by FOLFIRI regimen vs. FOLFIRI followed by FOLFOX regimen. A response rate of 15% and a median progression-

free survival of 4.5 months were seen in patients who progress to FOLFIRI chemotherapy when treated with FOLFOX, and a response rate of 4% with a median progression-free survival of 2.5 months for the reverse sequence [23].

The US Cooperative Groups completed a randomised intergroup clinical trial for the first treatment of advanced colorectal cancer. This trial was originally launched to compare IFL, FOLFOX and a combination of oxaliplatin and CPT-11 with Mayo regimen. A total of 795 patients were randomised. With a median follow-up of 20.4 months, all outcome measures for FOLFOX were significantly better than IFL, including a significantly better time-to-tumour progression (8.7 vs. 6.9 months, p=0.0014), a higher response rate (45% vs. 31%, p=0.002) and an improved overall survival (19.5 vs. 15 months, p=0.0001). Patients treated with irinotecan and oxaliplatin (IROX) had a significantly lower median time-to-progression (6.5 months) and response rate (35%) compared to FOLFOX (p=0.001 and p=0.03, respectively); median survival, however, did not differ significantly between the 2 regimens (19.5 vs. 17.4 months, p=0.09).

The results of this study establish the FOLFOX regimen as the first-line treatment in advanced col-orectal cancer [24].

The last generation of trials evaluated the triplet combination of CPT-oxaliplatin-FU in patients with newly diagnosed or pretreated metastatic colorectal cancer. A biweekly regimen with oxaliplatin, CPT-11, infusional FU and LV (FOLFOXIRI) showed a response rate of 71.4% and 26% of patients were downstaged and surgical resection could be performed; median progression-free and overall survival times were 10.4 and 26.5 months, respectively. The pharmacokinetics parameters of the agents used and their metabolites did not seem to be influenced by the concomitant use of the other drugs. The most relevant toxicities were diarrhoea and neutropenia [25] (Table 4).

Table 4. Comparative, sequential and integrated trials of CPT and OXA

Author

Trial

Response rate

Progression-free survival

Median survival

(%)

(months)

(months)

Tournigand et al. [23]

FOLFOX-FOLFIRI

56

8.1

20.4

FOLFIRI-FOLFOX

57.5

8.5

21.5

Goldberg et al. [24]

IFL

31

6.9

15

FOLFOX

45 pS

8.7 pS

19.5

IROX

34

6.5

17.4

Falcone et al. [25]

FOLFOXIRI

71.4

10.4

26.5

pS, p value statistically significant pS, p value statistically significant

Was this article helpful?

0 0
Dealing With Erectile Dysfunction

Dealing With Erectile Dysfunction

Whether you call it erectile dysfunction, ED, impotence, or any number of slang terms, erection problems are something many men have to face during the course of their lifetimes.

Get My Free Ebook


Post a comment