1. Concurrent chemotherapy and hyperthermia in patients with recurrent cervical cancer after chemoradiation: outcome and survival
S.T. Heijkoop1,2; H.C. van Doorn1; I.A. Boere3 ; M. Franckena2; J. van der Velden4; L.J.A. Stalpers5 ; A.M. Westermann6
1Obstetrics and Gynaecology , 2Radiation Oncology and Hyperthermia Unit ,3Medical Oncology Erasmus Medical Centre Rotterdam, the Netherlands, 4Obstetrics and Gynaecology , 5Radiation Oncology, 6Medical Oncology, Amsterdam Medical Centre, Amsterdam, The Netherlands
Background and aim
Cervical cancer is the third most common cancer worldwide in women. Patients with recurrent disease have a poor prognosis. When disease recurs in a previously irradiated area, the prognosis is particularly poor. Standard treatment of recurrent disease in previous irradiated areas consist of platinum-based chemotherapy. In earlier studies we showed that hyperthermia added to chemotherapy improved survival rates with response rates of 50-55%. At that time most women did get radiation only and they were chemo-naive at time of recurrence. In this study we evaluated whether the positive outcome of cisplatin based chemotherapy with concurrent hyperthermia also applied to patients with recurrent cervical cancer who received (cis) platin in first line treatment.
Material and methods
From the hyperthermia database of the Amsterdam Medical Centre and the Erasmus Medical Centre 38 patients were selected. Patients had had platinum based chemoradiation, or neoadjuvant chemotherapy followed by surgery and radiotherapy in first line. As by protocol all patients with recurrent cervical cancer received 6 or 8 platinum-based chemotherapy cycles in combination with 6 or 8 hyperthermia sessions. The time-to-event variables were estimated using the Kaplan-Meier analysis. P-values less than 0.05 were considered significant.
Results
Mean age of the patients at relapse was 45.7 years (range 24-74). Twenty patients had locoregional recurrence and four patients had distant metastases. Median time to recurrence after first line treatment was 15 months (table 1). 17/38 patients received all six or eight courses of cisplatin chemotherapy depending on hospital policy. The median follow-up time after treatment was 6.5 months. The incidence of grade 3 – 4 hematologic complications did not exceed 10%. Clinical response was poor with progressive disease in 19/38 patients (table 2). Overall survival at 12 months was 23%.
Table 3 . Vascular events during chemotherapy 1
Table 1. Patient characteristics
Table 2 . Clinical response N
Age, at primary diagnose
(years, range)
44.2 ( )
Age, at relapse (years, range)
45.7 ( )
Time to recurrence
(months median, range)
15 (3 – 62)
Histological type
Planocellulair carcinoma
Adenocarcinoma 34 4
FIGO stage primary tumor
IA2
IB1
IB2
IIA IIB
IIIA
IIIB
IVA
IVB 1 3 15 2 9
Previous treatment
Neoadjuvant chemotherapy
Surgery followed by neoadjuvant
chemotherapy or radiation
Chemoradiation 8 27
Site of recurrence
Loco-regional
Iliacal nodes
Para-aortic nodes
Distant 21 6 7
After first treatment (chemoradiation)
After chemotherapy and hyperthermia for recurrence CR 29 1 PR 9 4 PD - 19 SD 13
Figure 1. Overall Survival
Discussion & Conclusion
In this retrospective study concurrent treatment with cisplatin and hyperthermia after first line cisplatin containing chemotherapy and radiation gives a poor response. When patients only received radiotherapy as first line treatment, patients have response rates of 50-55% with chemotherapy and hyperthermia. However, it seems that with these poor response rates adding hyperthermia to chemotherapy is not a therapeutic option in patients with recurrent cervical cancer. New treatment options and prospective studies are urgently needed.
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