title: Topotecan plus ifosfamide in patients with platinum refractory advanced/metastatic non-small cell lung cancer: a phase II trial.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Oncology Institute, Via Amendola 209, 70126 Bari, Italy. lorusso@email.it
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Spada
authors.forename: Michele
authors.initials: M
authors.lastname: Guida
authors.forename: Grazia
authors.initials: G
authors.lastname: Cassano
authors.forename: Cosimo
authors.initials: C
authors.lastname: Brunetti
authors.forename: Domenico
authors.initials: D
authors.lastname: Germano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nettis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Izzi
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.forename: Marianna
authors.initials: M
authors.lastname: Giampaglia
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
mesh_terms: D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010984:Platinum / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D010984:Platinum; D019772:Topotecan; D007069:Ifosfamide