Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study.
BACKGROUND
Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer.


METHODS
120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute--Common Toxicity Criteria.


RESULTS
55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7-58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy.


CONCLUSIONS
A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease.
Pignata
Sandro
S
Medical Oncology B, National Cancer Institute, Naples, Italy. sandro.pignata@fondazionepascale.it
De Placido
Sabino
S
Biamonte
Rosalbino
R
Scambia
Giovanni
G
Di Vagno
Giovanni
G
Colucci
Giuseppe
G
Febbraro
Antonio
A
Marinaccio
Marco
M
Lombardi
Alessandra Vernaglia
AV
Manzione
Luigi
L
Cartenì
Giacomo
G
Nardi
Mario
M
Danese
Saverio
S
Valerio
Maria Rosaria
MR
de Matteis
Andrea
A
Massidda
Bruno
B
Gasparini
Giampietro
G
Di Maio
Massimo
M
Pisano
Carmela
C
Perrone
Francesco
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D019772:Topotecan / Q000008:administration & dosage
D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel