Eribulin Mesylate as Third or Subsequent Line Chemotherapy for Elderly Patients with Locally Recurrent or Metastatic Breast Cancer: A Multicentric Observational Study of GIOGer (Italian Group of Geriatric Oncology)-ERIBE.

BACKGROUND: Metastatic breast cancer (MBC) is highly prevalent in middle-aged or elderly patients. Eribulin is a nontaxane microtubule inhibitor, approved for the treatment of pretreated MBC. This multicentric study (sponsored by GIOGer, Italian Group for Geriatric Oncology) was designed to assess the efficacy and tolerability of eribulin, according to parameters usually used in geriatric oncology. SUBJECTS, MATERIALS, AND METHODS: An observational study was conducted on 50 consecutive elderly patients with MBC. The primary endpoint was to evaluate the change in items score of comprehensive geriatric assessment (CGA) and health-related quality of life (HRQL). Italian versions of the CGA and HRQL questionnaires were administered at baseline, before the third and fifth cycles, and then every three cycles until treatment discontinuation. Secondary endpoints were efficacy and safety. RESULTS: Overall, both EQ-5D scores and EQ-5D-3 L visual analogic scale did not significantly change from baseline; the percentage of subjects without problems doing usual activities tended to decrease during treatment (p for linear trend .018), and the percentage of patients with minor problems performing usual activities tended to increase (p for linear trend.012). Among CGA items, Instrumental Activities of Daily Living tended to decrease during treatment and Geriatric Depression Scale tended to increase. After 12 months follow-up, 24 patients (out of 47) showed clinical benefits; median progression-free survival was 4.49 months (2.10-10.33) and median OS was 7.31 months (3.70-14.03). The treatment was associated with mild toxicity. CONCLUSION: Eribulin treatment preserved quality of life and geriatric parameters included in the CGA, except for instrumental functioning and geriatric depression, in elderly patients with MBC. IMPLICATIONS FOR PRACTICE: A collaboration between oncologist and geriatric specialists is essential in the management of patients with metastatic breast cancer, who are frequently elderly or frail. The assessment of geriatric parameters in the decision-making process can contribute to direct toward the most appropriate therapeutic plan and preserve the quality of life of patients. Eribulin does not seem to affect quality of life or worsen the overall geriatric status; therefore, it can be considered a suitable option for elderly patients with metastatic breast cancer.

Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale.

PURPOSE: We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. PATIENTS AND METHODS: A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2 regimen). RESULTS: One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respectively), duration of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15 months, respectively) were similar, without any statistically significant difference. Toxicity was mild in both groups: alopecia and gastrointestinal disturbances were the most common toxicities in arm A; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms, and no statistical significant difference was observed. CONCLUSION: There is no difference in ORR, TTP, and OS for patients treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as first-line treatment in these patients. The difference between these two combination therapies is mainly in the toxicity profile.

Topotecan in the treatment of brain metastases. A phase II study of GOIM (Gruppo Oncologico dell'Italia Meridionale).

BACKGROUND: Topotecan is able to cross the blood-brain barrier (BBB) and has been demonstrated to be active in brain metastases from small cell lung cancer (SCLC). PATIENTS AND METHODS: The aim of this study was to evaluate the efficacy and toxicity of topotecan at a dosage of 1.5 mg/m2 for 5 consecutive days every 3 weeks in patients with brain metastases from various neoplasms. RESULTS: Among the 19 patients enrolled, objective responses were observed in 2 out of 3 patients affected by brain metastases from SCLC. Stable disease was observed in 8 more patients (4 breast, 3 non-SCLC and 1 colon). According to the Simon two-step design, patient accrual was stopped because of the low response rate observed in the first 19 patients treated (early stopping rule). The G 3/4 haematological toxicity was severe, with 37% neutropenia, 21% thrombocytopenia and 16% anaemia, respectively. CONCLUSION: Our data do not support the use of topotecan in patients with brain metastases, except for SCLC. In addition, the haematological toxicity prevents the use of this regimen in elderly and poor performance status patients.

Topotecan plus ifosfamide in patients with platinum refractory advanced/metastatic non-small cell lung cancer: a phase II trial.

A number of second line treatments have been proposed in patients with advanced pretreated non-small cell lung cancer (NSCLC). However, either single agents or two or three drug combinations achieved very poor results with no superiority of any combination over monotherapy. We have treated 42 patients (30 males) affected by advanced/metastatic NSCLC progressing during front line cisplatin-based chemotherapy with a combination of topotecan (1.2 mg/m2) plus ifosfamide (1200 mg/m2) for 3 consecutive days every 3 weeks. The median age was 63 years (range 43-76); cell types were: squamous carcinoma (n=17), adenocarcinoma (n=16), large cell carcinoma (n=3), broncho-alveolar carcinoma (n=2) and undifferentiated carcinoma (n=4). All patients were treated with a platinum containing chemotherapy: 39 patients with cisplatin, 2 patients with carboplatin and 1 patient with oxaliplatin, respectively. The ECOG PS was 0 in 8 patients (19%), 1 in 11 patients (26%), and 2 in 23 patients (55%). The median number of courses administered was 3 (range 1-8). Grade 3-4 neutropenia was the dose limiting toxicity, observed in 36% of patients. Moreover, grade 3-4 anemia and thrombocytopenia were observed in 17% and in 12% of patients, respectively. One PS 2 patient died of grade 4 hematological toxicity after the first cycle. No complete response was observed. Six (14.2%) subjects obtained a partial response (PR). In addition, 1 (2.4%) minimal response (MR) plus 14 (34%) stable diseases (SD) and 21 (51%) progressive diseases (PD) were observed. Median time to disease progression and median survival were 9 weeks (range 1-13) and 26 weeks (range 1-91+), respectively. The 1-year survival rate was 14%. Combination of topotecan and ifosfamide demonstrated antitumor activity in patients with relapsing or refractory NCSLC with a modest side effect profile and an overall disease control (PR + MR + SD) of 50.7%. Nevertheless, the still low response rate and the shortness of median survival indicates the need for more effective second line treatments in this disease.

Italian Survey on adjuvant treatment of non-small cell lung cancer (ISA).

BACKGROUND: A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours. PATIENTS AND METHODS: To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail. RESULTS: Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians. CONCLUSIONS: A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen.

Weekly dose-dense cisplatin-epirubicin-paclitaxel administration with granulocyte colony-stimulating factor support does not substantially improve prognosis in extensive disease small-cell lung cancer. A SICOG phase II study.

PURPOSE: The present study was aimed at defining the antitumor activity of the cisplatin-epirubicin-paclitaxel (PET) weekly administration with granulocyte colony-stimulating factor (G-CSF) support in chemonaive small-cell lung cancer patients with extensive disease (ED-SCLC). METHODS: Chemonaive ED-SCLC patients received cisplatin 30 mg/sqm, epirubicin 50 mg/sqm and paclitaxel 120 mg/sqm, weekly, with G-CSF (5 microg/kg from day 3 to 5) support, for a maximum of 12 weeks. RESULTS: Thirty-nine patients were treated, for a total of 354 cycles delivered. Eight complete (21%), and 22 partial responses (56%) were recorded, giving a 77% (95% CI = 61-89%) objective response rate (ORR). After 14 (range, 7-28)-month median follow-up, 24 deaths have occurred. Median progression-free and overall survival were 7 months and 11 months, with 1- and 2-year projected survivals of 45 and 24%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 4 (10%) and 1 (3%) patients, respectively. Only one case of neutropenic sepsis was recorded, while hemorrhagic thrombocytopenia was never observed. Emesis, loss of appetite, mucositis and fatigue were the main nonhematological toxicities, being severe in 9, 8, 4 and 7 patients, respectively. CONCLUSIONS: The weekly PET combination with G-CSF support represents an active therapeutic approach in chemonaive ED-SCLC patients. However, both ORR and median survival does not seem substantially better than those achievable with a standard regimen. In view of that, and in consideration of the relevant nonhematological toxicity, this approach should not be pursued outside clinical trials.