Gastric cancer: Chemotherapy of advanced disease

Macdonald, John S.

doi:10.1002/hon.2900100108

Cited by 18 publications

(7 citation statements)

References 15 publications

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“…Furthermore, given that many of the patients are diagnosed when the disease is unsuitable for curative surgery, there is a pressing need to develop better systemic therapies in adjuvant, neoadjuvant and metastatic settings (Macdonald et al, 1992).…”

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confidence: 99%

FEP regimen (epidoxorubicin, etoposide and cisplatin) in advanced gastric cancer, with or without low-dose GM-CSF: an Italian Trial in Medical Oncology (ITMO) study

et al. 1998

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Summary The new regimens developed over the last few years have led to an improvement in the treatment of advanced gastric cancer, and our previous experience confirmed the fact that the combination of etoposide, doxorubicin and cisplatin (EAP regimen) is an active treatment that leads to interesting complete remission rates. The primary end point of the present multicentre, randomized, parallel-group phase 11 study was to determine the activity of the simplified 2-day EAP schedule in patients with locally advanced or metastatic gastric cancer, and to verify whether the addition of low doses of granulocyte-macrophage colony-stimulating factor (GM-CSF) made it possible to increase dose intensity.Of the 62 enrolled patients, 30 were randomized to receive epirubicin 35 mg m-2, etoposide 120 mg m-2 and cisplatin 45 mg m-2 (FEP) on days 1 and 2 every 28 days and 32 to receive the same schedule plus subcutaneous GM-CSF (molgramostin) 150 ,ug day-1 on days 5-14 every 21 days. The patients were stratified by age and the number of disease sites. The characteristics of the patients were well balanced between the two groups. The objective response rate of the patients as a whole was 34% (21 out of 62; 95% confidence interval 22-46), with only one complete remission. The median response duration was 4.5 months (range 1-24 months). The median time to treatment failure was 5 months (range 1-14 months), without any difference between the two groups. The median survival of the patients as a whole was 9 months. Full doses were administered in 92% and 94% of the cycles in the control and GM-CSF arms respectively. The average dose intensity calculated for all drugs was 0.96% in the control and 1.27% in the GM-CSF group. CTC-NCI grade 3-4 neutropenia was reported in 39% vs 45% of patients, thrombocytopenia in 11% vs 35% (P = 0.020) and anaemia in 7% vs 35% (P = 0.014). The FEP combination is as active (OR: 34%) in the treatment of patients with advanced gastric cancer as the EAP regimen, although it leads to fewer complete remissions. The patients randomized to receive low-dose GM-CSF achieved a significantly higher dose intensity than controls (P = 0.0001).Keywords: polychemotherapy; gastric cancer; growth factor Although the incidence of gastric cancer seems to have declined regularly in Western countries over the last decade, it is still one of the leading causes of death worldwide (Moller et al, 1990). Furthermore, given that many of the patients are diagnosed when the disease is unsuitable for curative surgery, there is a pressing need to develop better systemic therapies in adjuvant, neoadjuvant and metastatic settings (Macdonald et al, 1992).The development of new chemotherapeutic regimens for the treatment of advanced gastric cancer, including cisplatin (CDDP), and anthracycine, or fluorouracil and high-dose methotrexate (EAP, FAMTX, ECF), has led to objective responses (OR) in 30-40% of the patients, with a complete remission (CR) rate of 10-15% (Wils et al, 1986;Preusser et al, 1989;Findlay et al, 1994;Rougier et al, 199...

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confidence: 99%

FEP regimen (epidoxorubicin, etoposide and cisplatin) in advanced gastric cancer, with or without low-dose GM-CSF: an Italian Trial in Medical Oncology (ITMO) study

et al. 1998

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“…1983; Machover et al . 1986; MacDonald 1992) and the synergistic activity of 5‐FU and cisplatin (Kim et al . 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The choice of drugs in this trial was based on their single-agent activity in upper-gastrointestinal cancers (Beer et al 1983;Machover et al 1986;MacDonald 1992) and the synergistic activity of 5-FU and cisplatin (Kim et al 1993). We obtained a PR rate of 11.3% and 1-year OS rate of 11.32% with this regimen.…”

Section: Discussionmentioning

confidence: 99%

The symptomatic benefit (the clinical benefit response) from the second-line chemotherapy in patients with advanced gastric adenocarcinoma

et al. 2007

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There are few reports on use of symptomatic benefits as an alternative or adjunctive for the assessment of objective response in chemotherapy of the advanced cancer. This study is performed to assess the symptomatic benefits (the clinical benefit response), in addition to the efficacy and toxicity of cisplatin plus infusional 5-fluorouracil (5-FU) combination as second-line therapy in patients with advanced gastric cancer. Fifty-eight advanced gastric cancer patients with previous chemotherapy were enrolled into the study. Cisplatin 20 mg/m(2) was given for 5 days, and 5-FU was given 1000 mg/m(2) as 20 h continuous infusion for 5 days, repeated every 28 days. The overall objective response rate was 11.3%, and overall tumour control rate was 33.9%. The clinical benefit response, in terms of weight gain, reduction in analgesic consumption and the improvement in performance status observed in 12 patients [six patients with partial response (PR) and six patients with stable disease (SD)] (22.6%), while the rates of the clinical benefit response in patients with PR and with SD were 100% and 50% respectively. Cisplatin plus infusional 5-FU combination seems to improve disease-related symptoms (clinical benefit response) of patients with advanced gastric cancer, even in patients without objective response.

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“…The degree of necrosis and its prognostic significance depend upon numerous factors and are classified according to the neoplastic histology and the specific anatomic substrate [13]. For example, chemotherapy-induced necrosis in neoadjuvant therapy of osteosarcomas must be superior to 90% of the lesion volume to be regarded as prognostically favorable, whereas in other neoplasms (gastric and breast carcinomas) lower ratios, always during neoadjuvant courses, may still constitute satisfactory results [27,28,29,30,31,32]. Local treatment of hepatocellular carcinomas represents one of the most extensively studied models for the definition of imaging parameters related to therapy-induced tumor necrosis [33,34,35,36].…”

Section: Necrosismentioning

confidence: 99%

Structural changes induced by antineoplastic therapies: keys to evaluate tumor response to treatment

2001

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The criteria to define therapeutic response in oncology are those proposed by Miller, characterized by four response categories (complete response, partial response, no change, progression of disease), and based upon both measurable and non-measurable (and otherwise assessable) morphological parameters in comparison with baseline and subsequently modified following the Response Evaluation Criteria In Solid Tumors. In addition to these classical morphological criteria, we review the predictive value of structural changes in the evaluation of response to antineoplastic therapies. The goal of the present review is to evaluate in detail structural variations (calcification, fibrosis, differentiation, necrosis, cavitation, vascularization, edema, and pseudocapsule formation) induced by therapy, and to ascertain their significance in terms of biological evolution of the neoplastic process.

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Gastric cancer: Chemotherapy of advanced disease

Cited by 18 publications

References 15 publications

FEP regimen (epidoxorubicin, etoposide and cisplatin) in advanced gastric cancer, with or without low-dose GM-CSF: an Italian Trial in Medical Oncology (ITMO) study

FEP regimen (epidoxorubicin, etoposide and cisplatin) in advanced gastric cancer, with or without low-dose GM-CSF: an Italian Trial in Medical Oncology (ITMO) study

The symptomatic benefit (the clinical benefit response) from the second-line chemotherapy in patients with advanced gastric adenocarcinoma

Structural changes induced by antineoplastic therapies: keys to evaluate tumor response to treatment

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