The prognostic value of a response to chemotherapy given before radiotherapy in advanced cancer of cervix

Abstract

Summary Forty patients with stage III and 15 patients with stage IVa carcinoma of cervix have been treated with two pulses of cisplatin, vincristine and bleomycin combination chemotherapy before full dose radical radiotherapy. Twenty-seven of 51 (53%, 95% confidence interval 40-67%) had an objective response to chemotherapy and all chemotherapy responders had a complete response to radiotherapy. The actuarial survival at 24 months of responders to chemotherapy is 71% against 37% for non-responders. The responding patients had an estimated reduction in mortality to 36% (P=0.014, 95% CI 15-81%) of that of the non-responders to chemotherapy. The incidence of tumour recurrence or distant metastases showed a similar reduction to 34% (P=0.006, 95% CI 14-73%) of that of the non-responders. The data strongly suggest that response to chemotherapy in the initial treatment of advanced cervical cancer is associated with an improvement in survival following subsequent radical radiotherapy.Both clinical studies (Shukovsky & Fletcher, 1973) and animal experiments (Fowler et al., 1963) have shown that radiation doses that will consistently eradicate small tumours will only be effective in a minority of larger lesions. The maximum radiation dose that can be given to patients with advanced carcinoma of cervix is limited by the tolerance of surrounding organs, such as the bladder and bowel.Even employing what are currently regarded as optimal fraction policies in combination with intracavity treatment, local control is achieved in only about half of patients with advanced carcinoma of cervix. Typical local recurrence-free rates are 51% for stage III (Adams & Kerby, 1983) and 43% for stage IVa patients (Upadhyay et al., 1988). The relative radio-resistance of bulky tumours may in part be due to the presence of hypoxic cells within the tumour as radiotherapy in hyperbaric oxygen increased local control in one large randomised series (Watson et al., 1978), but other factors could also be important. Local control using conventional radiotherapy schedules may be increased if the tumour size could be reduced by chemotherapy given before radiotherapy. Advanced carcinoma of cervix may be particularly susceptible to this approach as the tumour is moderately chemosensitive (Guthrie, 1985) and a proportion of lesions which are locally far advanced may not have spread beyond the true pelvis.As a first step to testing this hypothesis we carried out a pilot study of cisplatin-based chemotherapy given before full dose radiotherapy. Materials and methodsThe first 55 patients who entered this pilot study have been followed up for up to 51 months since the end of treatment (median follow-up 21 months). Forty patients were assigned to stage III and 15 to stage IVa; all had squamous carcinomas. All the relevant biopsy material has been retrospectively reviewed (without knowledge of which patients responded to chemotherapy) using the grading system of Reagan & Wentz (Gunderson et al., 1974). The mean age of patients was 49 years (range 29-70) and all ...

Neoadjuvant chemotherapy with cisplatin, ifosfamide and 5-fluorouracil in the treatment of locally advanced cervical cancer

“…In fact, patients with tumors which did not respond had a significantly worse five-year survival rate than those with responding tumors; none of the patients with nonresponsive tumors even became free of disease after radiotherapy. Such a relationship between failure to respond to chemotherapy and radioresistance has also been observed by other authors (5,24,25) . The biological reasons still remain to be clarified; in vitro models suggest that chemoradioresistance might be an innate characteristic of some tumors (26) or that cell kinetic changes following chemotherapy may contribute to treatment failure in the irradiated volume (27) .…”

Patterns of treatment failure following radiotherapy with combination chemotherapy for patients with high-risk stage IIB cervical carcinoma

“…7 With this discouraging outcome in mind, efforts have been made to improve tumor control by adding chemotherapy, thus expecting theoretical synergistic benefits. 13,14 Increasing evidence indicates the superiority of concurrent chemotherapy and radiation therapy over radiation alone in overall survival and progression-free survival. 15,16 In our previous study with 386 patients with bulky stages I-II cervical cancer, 5 the 30-month survival rates were 100% and 79.5% following concurrent chemoradiation and radiation alone, respectively, providing evidence for the superiority of concurrent chemotherapy and radiotherapy to radiation alone.…”

Carcinoma of the cervix: an analysis of prognostic factors, treatment and patterns of failure following Wertheims hysterectomy

“…Previous attempts to extend the radiotherapy field to include the para-aortic areas and to deliver effective doses to this area in continuity with the pelvis have been associated with high morbidity and mortality (is). Recent experience has suggested improved results with the addition of chemotherapy to radiotherapy in the treatment of advanced carcinoma of the cervix (5). We would suggest consideration of the use of adjuvant chemotherapy in those patients who have nodal involvement at the time of initial surgery.…”

“…similarly been used in the management of recurrent carcinoma of the cervix and recently its role as an adjuvant therapeutic modality in patients with advanced stage carcinoma of the cervix has been studied (5).…”