ASCO: Chemotherapy Holiday Not Recommended for Metastatic Colorectal Cancer

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CHICAGO -- Time off from chemotherapy early in oxaliplatin (Eloxatin)-based treatment for metastatic colorectal cancer may reduce toxicity but impair survival, researchers said.

CHICAGO, June 7 -- Time off from chemotherapy early in oxaliplatin (Eloxatin)-based treatment for metastatic colorectal cancer may reduce toxicity but impair survival, researchers said.

Continuous leucovorin (Wellcovorin) and 5-fluorouracil therapy after oxaliplatin-based chemotherapy tended to yield better progression-free survival (8.2 versus 6.7 months) and longer overall survival (26 versus 19 months) than chemotherapy-free intervals, found Frederique Maindrault-Goebel, M.D., of Hpital Saint-Antoine in Paris, and colleagues.

"Preserving quality of life is a strong rationale to study a chemotherapy-free interval," Dr. Maindrault-Goebel said at the American Society of Clinical Oncology meeting here.

Yet, she added, "despite the advantages for the patients, a full break in therapy cannot be recommended based on the results of this study."

Previously, the OPTIMOX1 trial showed similar disease control and survival outcomes but lower toxicity with an oxaliplatin-free interval after FOLFOX7 (oxaliplatin, fluorouracil, and leucovorin) compared with continuous FOLFOX4 chemotherapy.

To see whether maintenance therapy was necessary in a "stop and go" strategy, the researchers conducted the OPTIMOX2 trial.

It included 202 patients with metastatic colorectal cancer who underwent six cycles of a modified FOLFOX7 regimen, which consisted of 400 mg/m2 leucovorin, 3,000 mg/m2 5-fluorouracil, and 100 mg/m2 oxaliplatin.

The same regimen was reintroduced at disease progression. In the interval between, patients were randomized to receive either no maintenance therapy or continued therapy minus oxaliplatin.

Maintenance therapy included a mean of eight cycles.

The median chemotherapy-free interval was about 17 weeks overall. There was no difference in interval duration between those with good or poor prognosis (P=0.38) or initial response or stable disease (P=0.31).

Among the results, partial and complete response was similar between groups (60% versus 59%).

Progression-free survival tended to be better in the maintenance arm (8.2 versus 6.7 months, P=0.08).

The duration of disease control, defined as the time without progressive disease, was not significantly different between groups but favored maintenance therapy (12.0 versus 9.0 months, P=0.39).

Overall survival likewise tended to be longer with maintenance therapy (26 versus 19 months, P=0.0549).

FOLFOX7 chemotherapy had "good" tolerance in both groups initially with Grade 3-4 neutropenia at 12% to 19% and Grade 3-4 thrombocytopenia at 4% to 12%.

During maintenance therapy, fewer than 10% of patients had any Grade 3-4 toxicity.

During the two months after FOLFOX7 treatment, Grade 3-4 neuropathy was similar between groups at 2% with maintenance therapy and 3.9% with chemotherapy-free intervals.

The researchers concluded that full chemotherapy-free intervals cannot be recommended early in therapy.

"A shorter break, a later break, or intermittent chemotherapy .?deserve to be evaluated," Dr. Maindrault-Goebel said, "and now the option is to have maintenance therapy without chemotherapy."

An ongoing study is looking at this option with targeted therapy alone for maintenance, she said.

Oncologists are now faced with a number of strategies for colorectal cancer recapitulating those tested in breast cancer, said Jean Grem, M.D. of the University of Nebraska Medical Center in Omaha, who was a discussant for the OPTIMOX2 presentation.

"Part of this is that in treating colorectal cancer we were limited for many years to 5-fluorouracil alone and then modulation of 5-fluorouracil," she said.

"So now the tendency is let's put everything together as in the FOLFOXIRI regimens and now with our combination regimens adding bevacizumab [Avastin] with or without cetuximab [Erbitux] or potentially panitumumab [Vectibix]," she added

Another other challenge will be incorporating prognostic and predictive factors to select the appropriate strategy for individual patients, Dr. Grem said.