title: Weekly topotecan and cisplatin (TOPOCIS) as neo-adjuvant chemotherapy for locally-advanced squamous cervical carcinoma: Results of a phase II multicentric study.
abstract: OBJECTIVE
  The aim of this phase II multicentric study was to evaluate the efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and cisplatin in locally-advanced squamous cervical cancer.
  
  
  METHODS
  From November 2008 to January 2011, 92 patients met the inclusion criteria and were enrolled. Eligibility criteria were: squamous or adenosquamous cervical cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)≤ 2; neutrophils ≥1500/μL; platelets ≥100,000/μL, normal renal and liver function. Treatment consisted of six courses of weekly topotecan (2mg/m(2)) and cisplatin (40 mg/m(2)). All responsive and stable patients were submitted to radical surgery, while progressed cases underwent definitive radiotherapy±chemotherapy. Primary end-point was evaluation of efficacy and toxicity. All patients are evaluable for toxicity and efficacy.
  
  
  RESULTS
  Ninety-six percent of patients completed the six planned courses of chemotherapy, and 95% of courses were administered at a full dose and without interruption or delay. Mean age was 49 years (35-64 years). FIGO Stage distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no death occurred. G3-G4 haematological toxicity was observed in 28% of patients (5% out of cycles). Support therapies (blood transfusions and/or erythropoietin and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients. Clinical response rate was 77%. The nine progressed cases were irradiated, while the remaining 83 patients were submitted to radical surgery. An overall pathologic response was observed in 67% of patients, with an optimal response rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was prescribed in 55% of patients, because of lymph node metastases, parametrial or vaginal involvement or cut-through margins. Median follow-up was 18 months: 76% of patients are alive and free from recurrence, 24% of patients relapsed and 13% died.
  
  
  CONCLUSIONS
  Weekly topotecan and cisplatin showed an acceptable toxicity profile; the promising response rate warrants further investigation.
authors.affiliation: Gynecologic Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, via Venezian no.1, Milan, Italy. flavia.zanaboni@istitutotumori.mi.it
authors.forename: F
authors.initials: F
authors.lastname: Zanaboni
authors.forename: B
authors.initials: B
authors.lastname: Grijuela
authors.forename: S
authors.initials: S
authors.lastname: Giudici
authors.forename: G
authors.initials: G
authors.lastname: Cormio
authors.forename: L
authors.initials: L
authors.lastname: Babilonti
authors.forename: F
authors.initials: F
authors.lastname: Ghezzi
authors.forename: G
authors.initials: G
authors.lastname: Giorda
authors.forename: G
authors.initials: G
authors.lastname: Scambia
authors.forename: M
authors.initials: M
authors.lastname: Franchi
authors.forename: M
authors.initials: M
authors.lastname: Lorusso
authors.forename: A
authors.initials: A
authors.lastname: Ditto
authors.forename: D
authors.initials: D
authors.lastname: Lorusso
authors.forename: F
authors.initials: F
authors.lastname: Raspagliesi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D019772:Topotecan; D002945:Cisplatin