Metronomic oral chemotherapy with cyclophosphamide plus capecitabine combined with trastuzumab (HEX) as first line therapy of HER-2 positive advanced breast cancer: A phase II trial of the Gruppo Oncologico Italia Meridionale (GOIM)
Laura Orlando,
Vito Lorusso,
Francesco Giotta,
Massimo Di Maio,
Paola Schiavone,
Palma Fedele,
Annamaria Quaranta,
Chiara Caliolo,
Mariangela Ciccarese,
Margherita Cinefra,
Sante Romito,
Salvatore Pisconti,
Salvatore del Prete,
Michele Aieta,
Daniele Rizzi,
Evaristo Maiello,
Giuseppe Colucci,
Saverio Cinieri
Affiliations
Laura Orlando
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy; Corresponding author. Oncology Division & Breast Unit, Antonio Perrino Hospital, 72100, Brindisi, Strada Statale 7 (Via Appia), Italy.
Vito Lorusso
Medical Oncology, Istituto Tumori Giovanni Paolo II, IRCCS, Bari, Italy
Francesco Giotta
Medical Oncology, Istituto Tumori Giovanni Paolo II, IRCCS, Bari, Italy
Massimo Di Maio
Department of Oncology, University of Turin at Ordine Mauriziano Hospital, Turin, Italy
Paola Schiavone
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy
Palma Fedele
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy
Annamaria Quaranta
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy
Chiara Caliolo
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy
Mariangela Ciccarese
Medical Oncology, Ospedale Vito Fazzi, Lecce, Italy
Margherita Cinefra
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy
Sante Romito
Medical Oncology, Ospedali Riuniti, Foggia, Italy
Salvatore Pisconti
Medical Oncology, Ospedale Moscato, Taranto, Italy
Salvatore del Prete
Medical Oncology, Ospedale San Giovanni di Dio, Frattamaggiore, Napoli, Italy
Michele Aieta
Medical Oncology, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza, Italy
Daniele Rizzi
Medical Oncology, Istituto Tumori Giovanni Paolo II, IRCCS, Bari, Italy
Evaristo Maiello
Medical Oncology, Ospedale Sollievo Della Sofferenza, IRCCS, San Giovanni Rotondo, Foggia, Italy
Giuseppe Colucci
Medical Oncology, Istituto Tumori Giovanni Paolo II, IRCCS, Bari, Italy
Saverio Cinieri
Medical Oncology, Antonio Perrino Hospital, Brindisi, Italy
Background. The combination of chemotherapy plus anti HER-2 agents is the mainstay of HER-2 positive advanced breast cancer (ABC) therapy. We conducted a phase II trial testing activity and safety of trastuzumab and metronomic capecitabine/cyclophosphamide (HEX) as first-line therapy in HER-2 positive ABC. Methods. Patients at first relapse or with synchronous metastasis were treated with trastuzumab (4 mg/kg, biweekly) plus oral capecitabine (1500 mg/daily) and cyclophosphamide (50 mg/daily). Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival (PFS), clinical benefit rate (CBR; PR + CR + SD for ≥ 24 weeks) and tolerability. Optimal two-stage design was applied. Results. Sixty patients with measurable ABC, tumors scored as +3 for HER-2 or FISH +, untreated for advanced disease were enrolled. Median age was 62.5 years, visceral metastases were present in most patients (57.9%). Median number of cycles was 16 (range 1–98). ORR was 56.7% (95% CI, 44.1–68.4%), with 5 CR (8.3%) and 29 PR (48.3%). Fifteen patients had SD (25%). The CBR was 78.2%. Nine progressions were observed (15%). Median PFS was 11 months. One year PFS was 47.7%. Median OS was 45.9 months. Worst toxicities were grade 3 hand-foot syndrome in 2 pts (3.3%), grade 3 anaemia in 2 pts (3.3%), grade 2 nausea in 2 pts (3.3%) and grade 3–4 diarrhea in 2 pts (3.3%). Cardiac toxicity grade 1 was reported in 1 pt. Conclusions. Combination of trastuzumab and metronomic oral chemotherapy has clinical activity. The tolerability was excellent and allowed the prolonged delivery of treatment.