The impact of cisplat based chemotherapy on advanced ovarian cancer.
GR Prasad, AV Dalal, HB Tongaonkar, S Chatterjee, MR Kamat
Gynecologic Oncology Service, Tata Memorial Hospital, Parel, Bombay.
G R Prasad
Gynecologic Oncology Service, Tata Memorial Hospital, Parel, Bombay.
Cisplatinum based chemotherapy has become the standard treatment for ovarian cancers due to its proved superiority over non-cisplat based regimes. However, the therapeutic impact of cisplat based regimes compared to cheaper non-cisplatinum based regimes is questionable when multiple variables such as residual disease, histologic type, grade are introduced. This report is a study of 110 Stage III ovarian cancer patients from 1985-89, with cisplat (n = 69) and non cisplat (n = 41) based chemotherapy. The results of both regimes with reference to the multiple variable factors are presented. We conclude that cisplat based regimes appear to be superior to non-cisplat based regimes except probably in poorly differentiated ovarian tumors where the results were similar with either regimen.
|How to cite this article:|
Prasad G R, Dalal A V, Tongaonkar H B, Chatterjee S, Kamat M R. The impact of cisplat based chemotherapy on advanced ovarian cancer. J Postgrad Med 1995;41:95-8
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Prasad G R, Dalal A V, Tongaonkar H B, Chatterjee S, Kamat M R. The impact of cisplat based chemotherapy on advanced ovarian cancer. J Postgrad Med [serial online] 1995 [cited 2022 May 18 ];41:95-8
Available from: https://www.jpgmonline.com/text.asp?1995/41/4/95/515
The majority of women with ovarian cancer present with advanced disease. Therefore, chemotherapy assumes an important role in addition to surgery as primary treatment. Though the role of chemotherapy in advanced ovarian cancer has been established, various chemo-therapeutic agents single or in combination have been tried producing varying response rates and survivals. Following the report of Wiltshaw and Kroner on the effectiveness of cisplatin in advanced ovarian cancer with response rates of 25% researchers at the University of Indiana reported a three drug combination of cisplatin, adriamycin and cyclophosphamide (CAP) as first line of chemotherapy in ovarian cancer.
Because of the higher cost and enormous patient load CAP is still out of reach of a majority of patients in developing countries. Besides, despite good clinical response rates the role of cisplat based chemotherapy in significantly prolonging survivals in advanced ovarian cancer is being questione. The therapeutic impact of cisplat based regimens in advanced ovarian cancer in comparison to other cheaper multi drug regimens needs to be confirmed with reference to prognostic factors like residual tumour size, histologic type and grade of tumour before final approval of cisplat based therapy against noncisplat regimens. The present report is an overall evaluation of cisplat based regimens and noncisplat based regimens with an aim to assess relative efficacy in reference to known prognostic factors.
All patients of Stage Ill ovarian cancer registered at the Tata Memorial Hospital between January 1985 and December 1989 and completed primary treatment consisting of abdominal hysterectomy and bilateral salpingoociphorectomy with or without omen-tectomy and at least six cycles of chemotherapy were included in the study. Clinical records and operative reports were reviewed to determine stage, grade, residual disease, response to treatment and survival. The amount of residual disease remaining at the end of primary surgery was determined from the operative report. Clinical complete response (C R) was defined as evidence of no disease by clinical methods at the time of completion of primary treatment. Clinical partial response was defined as evidence of disease of less than 50% volume at the completion of treatment. Evidence of more than 50% of volume of disease at the completion of treatment or increase in volume of disease any time during treatment at primary site or appearance of disease at distant site was recorded as no response/progressive disease. Residual disease at the completion of primary surgery was determined and recorded as 2 cm and less or more than 2 cm. Because of personal constraints on the part of patients, we were to offer cisplat based therapy to all patients to administration of other cheaper combination regimens in good number of patients. Cisplat based therapy consisted of cisplatinum 100 mg/m2, adriamycin 40 mg/ml and cyclophosphamide 600 mg/m2, while noncisplat based therapy included multi drug regimens like CMF (cyclophosphamide 400600 mg/m2, methotrexate 3040 mg/m2, 5fluorouracil 600 mg/m2), F A C(5-fluorouracil 600 mg/m2, adriamycin 40 mg/m2 cyclophospharnide 600 mg/m2). The allocation of the patients was in nonrandomised fashion. The patients receiving cisplatbased therapy were compared to those receiving noncisplat based therapy in relation to clinical drug response and 5year survival. The survival figures were calculated by the method of Kaplan and Meir all patients followed up till December 1991.
A total of 110 cases of Stage III were e-valuable registered during the period from January 1985 to December 1989. 69 patients received cisplat based therapy and 41 patients received noncisplat based therapy. The characteristics of patients under these two categories are given in [Table:1].
The various clinical responses of the patients in these two groups are given [Table:2]. The overall 5 year survival for Stage III ovarian carcinoma was 23.3%.
The overall 5 year survival following cisplat based therapy was 42%, whereas same following non-cisplat based therapy was 15% as depicted in [Figure:1] in relation to the status of residual disease at the end of primary surgery, 5 year survival was 57% with cisplat based therapy if the residual disease was < 2 cm, while the same with non cisplat based therapy was 12.5% as shown in [Figure:2]. When the residual disease was > 2 cm, with cisplat based therapy 5 year survival was 20%, while none survived at 5 years with noncisplat based therapy when residual disease was > 2 cm as shown in [Figure:3].
With cisplat based therapy endometrioid tumours had better survival (60%) compared to serious tumours (31 %) whereas with noncisplat based therapy 5 year survival was uniformly poor 17% and 14% respectively as shown in [Figure:4] & [Figure:5].
In relation to histo-logic grading of tumour with cisplat based therapy, well and moderately differentiated tumours had a 5 year survival of 38% while same with noncisplat based therapy with 29% as shown in [Figure:6]. With cisplat based therapy 5 year Discussion survival with poorly differentiated tumours was 17% whereas same with non cisplat based therapy was 13% as shown in [Figure:7].
During the last decade, the success of initial good response rates in advanced ovarian cancer have been credited to combination chemotherapy and cytoreductive surgery. These two modalities being complementary in the primary treatment of ovarian cancer. But it is still to be established whether these initial promising good responses with cisplat based therapy translate into lasting long-term survivals? Cost being an important concern in the developing countries concrete proof needs to be established about the therapeutic superiority of cisplat based therapy over cheaper noncisplat based therapy with reference to residual tumour volume, histologic type and grade. It we can determine the relative efficacy in important subsets, alternative cheaper regimens can be chosen in the subsets where cisplat based therapy does not offer superior results. In the present study, the efficacy of cisplatbased therapy in comparison to cheaper noncisplat based therapy was examined with special reference to some of the known prognostic variables.
An overall 5 year survival of 42% with cisplat based therapy as against 15% serves well to justify the persistence of clinical investigation with cisplat based regimens. Besides in the present study, cisplat based therapy produced better C R (84% vs 71 %) and decreased relapse rate (51% vs 68%) compared to other regimens. Several studies have reported that residual disease status at the end of primary surgery is an important prognostic variable which determines final outcome,,, in the ovarian cancer though this might indirectly be determined by biologic behaviour of tumour The cisplat based therapy appears to be superior to noncisplat based therapy both when residual disease was <2 cm (5 year survival 57% vs 13%) and when residual disease was > 2 cm (5 year survival 20% vs 0). In other words, survival was poor when residual disease was > 2 cm when noncisplat based therapy was used.
It had been reported that the histologic type of tumour as an important prognostic variable though some studies could not find any significance.. In the present study, endometrial tumours had better 5 year survival both with cisplat based therapy (67%) and noncisplat based therapy (17%) compared to serious tumours (31% with cisplat based therapy and 14% with noncisplat based therapy) though survivals were uniformly poor with noncisplat based therapy. None of the six patients with mucinous tumours survived 5 years.
The value of histologic grading as a prognostic variable in advanced ovarian cancer is still not established though there are reports that tumour grade is an important prognostic variable in early stages,. In the present study, well and moderately differentiated tumours had a better survival (38%) compared to poorly differentiated tumours (17%) with cisplat based therapy. But poorly differentiated tumours did poorly whether treated with cisplat based therapy or non-cisplat based therapy (5 year survivals of 17% and 13% respectively)
So, in conclusion cisplat based therapy appears to be worth pursuing even in developing countries. despite its higher cost in view of significantly better 5 year survival compared to other regimens. But patients of advanced ovarian cancer with poorly differentiated tumours may not derive superior benefit with cisplat based therapy alone and till the lime a better therapeutic modality is evolved and for patients who cannot afford, noncisplat based regimens can be suggested with equal efficacy.
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