Is third-line chemotherapy routine practice in recurrent or metastatic gastric cancer?

e15558 Background: Patients (pts) with recurrent or metastatic gastric cancer eventually experience disease progression during or after completion of first-line chemotherapy. Second-line therapy is generally recommended in the current guidelines. Although third-line therapy is often performed in daily practice in some countries, there are few reports about the benefit of third-line therapy. Methods: A retrospective review was conducted on 683 pts who underwent at least first-line palliative chemotherapy for recurrent (n = 297) or primary metastatic (n = 386) gastric cancer. Clinicopathological characteristics and overall survival (OS) were analyzed according to the lines of chemotherapy as well as for all study pts. Results: One hundred and forty-nine pts (21.8%) underwent third- or further-line therapy. Third- or further-line therapy was more frequently performed in pts with young age ( < 70) (p < 0.0001), ECOG PS 0 or 1 (p < 0.0001) at the initiation of first-line therapy, first-line combination regimen (p = 0.006), and palliative surgical resection before first-line therapy (p = 0.029). The median follow-up duration was 62 months (24-151 months) for the survivors. The median OS for pts after first- and third-line therapy was 10 and 6 months, respectively. The median OS of pts who received third-line therapy was significantly longer than that of pts who received second- or lesser-line therapy (18 vs. 8 months, p < 0.0001). Multivariate analysis revealed that third- or further-line therapy was independently associated with favorable OS (hazard ratio = 0.56, p < 0.0001) along with surgical resection (p < 0.0001) and first-line combination regimen (p = 0.008), whereas signet ring cell histology (p = 0.002) and peritoneal metastasis (p = 0.027) were independent prognostic factors of poor OS. Conclusions: This study suggests that recurrent or metastatic gastric cancer pts may benefit from third-line chemotherapy, although careful selection is essential.

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Phase II Study of S-1 Monotherapy as a First-line, Combination Therapy of S-1 plus Cisplatin as a Second-line, and Weekly Paclitaxel Monotherapy as a Third-line Therapy in Patients with Advanced Gastric Carcinoma

Clinical medicine Oncology ◽

10.4137/cmo.s610 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S610

Author(s):

Yasushi Rino ◽

Norio Yukawa ◽

Nobuyuki Wada ◽

Makoto Suzuki ◽

Hitoshi Murakami ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Effect ◽

Phase Ii Study ◽

Sequential Therapy ◽

Second Line ◽

First Line ◽

Line Therapy ◽

Third Line Therapy ◽

Third Line ◽

Line Chemotherapy

Background We conducted a pilot phase II study to evaluate the efficacy and safety of S-1 as a first-line, S-1 plus cisplatin as a second-line, and weekly paclitaxel as a third-line therapy for advanced gastric cancer. Patients and Methods Between 2002 and 2005, 19 patients were enrolled in this study. Chemotherapy consisted of either 60 mg/m2 of S-1 for 4 weeks at 6 weeks interval, a combination of 60 mg/m2 S-1 for 3 weeks and 60 mg/m2 cisplatin on day 8 at 5 weeks interval, or 60 mg/m2 paclitaxel at day 1, 8, 15, at 4 weeks interval. The regimen was repeated until the occurrence of unacceptable toxicities, disease progression, or patient refusal. The primary end point was the overall survival. Results The response rates were 33.3%, 12.5%, and 0% after the first, second, and third line chemotherapy, respectively. The mean overall survival time was 994 days. The median survival time could not be calculated because 12 out of 19 patients were still alive when the study was concluded. Regarding hematological toxicity, the major adverse effect was leukopenia, which reached grades 3–4 in all lines of chemotherapy investigated. In addition, regarding non-hematological toxicities, the major adverse effect was anorexia, which reached grade 3–4 in the second line chemotherapy, and no deaths were attributable to the adverse effects of the drugs. Conclusion This sequential therapy was an effective treatment for advanced gastric cancer with acceptable toxic side-effects. We considered this sequential therapy to be effective because of the smooth switch to the next regimen.

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