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Journal of Cancer Research and Therapeutics
Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI)
ISSN: 0973-1482 EISSN: 1998-4138
Vol. 3, Num. 3, 2007, pp. 150-152

Journal of Cancer Research and Therapeutics, Vol. 3, No. 3, July-September, 2007, pp. 150-152

Original Article

Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors

Attili VenkataSatya Suresh, Chandra RamaC, Anupama G, Loknath D, Bapsy PP, Dadhich HemantK, Babu GovindK

Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore - 560 029
Correspondence Address: Dr. AVS Suresh, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore - 560 029, India. E-mail: sureshattili@yahoo.com

Code Number: cr07039

Abstract

Background: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors.
Materials and Methods: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received.
Results: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP.
Conclusion: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Keywords: Bleomycin, etoposide, and cisplatin, cost-effectiveness analysis, metastatic germ cell tumors, VIP

In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However upto 20% of the cases of the germ cell tumors are not curable. [1] In such cases, various attempts have been made to improve the outcome, e.g., by increasing the dose of cisplatin, [2] increasing schedule intensity, [3] or by adding more drugs/using alternative regimens. [4] Till date none of these measures have demonstrated any clear superiority over the conventional BEP regimen. However, in one of the recently conducted studies, etoposide, cisplatin, ifosfamide (VIP) showed better CR rates compared to the BEP regimen (37% vs 31%; though this was not statistically significant), and the authors concluded that there is more toxicity with VIP and it does not provide any clear survival advantage. [5] Though exact statistics are not available from all parts of India, the percentage of patients presenting in advanced disease is far more than the 20% reported in West. In view of the large number of cases presenting in the advanced stage (high-risk cases) in India, a resource poor nation, we undertook this retrospective analysis in patients receiving either BEP or VIP as first-line therapy to examine and compare the toxicity and cost effectiveness of these regimens.

Materials and Methods

All male patients with germ cell tumors (high risk) attending the Kidwai Memorial Institute of Oncology (KMIO), Bangalore, between January 2002 and December 2004 were included in the study.

The inclusion criteria were:

  1. Proven case of poor-risk germ cell tumor
  2. Clinical, laboratory, and other details completely available
  3. Minimum follow-up of 2 years after completion of therapy
  4. Informed consent from the patient before any chemotherapy (a routine practice at our hospital)
The patients′ clinical, laboratory, and other data were collected from the records. The patients were stratified into two groups, depending on the type of chemotherapeutic regimen (BEP vs VIP) they received. Risk stratification and follow-up were done according to NCCN guidelines-2005. Out of the total of 52 diagnosed patients, complete details were available for 46 patients. While choosing the treatment modality, no fixed pattern was followed. However, in general, relatively young patients, with poor ECOG-Performance Status and having a higher tumor burden were allocated VIP and the others were allocated BEP. (For assessing tumor burden, no exact definition was followed; the decision was made by the treating oncologist based on the number of metastases or the levels of the serum markers). Cost of the therapy was calculated for all cycles of chemotherapy, including the management of complications. However cost for the follow-up and other investigations were not included, as we followed the same workup plan in both the treatment groups. Duration of hospital stay in both the groups included that for the chemotherapy administration and also any admission for management of complications. Each episode of grade 3 or 4 complication for each patient was calculated as a separate entity.

Statistical analysis

Mean cost of the therapy (as well as standard deviation) per patient was calculated in each group. Means were compared using the Student′s t test and the differences, with 95% confidence interval (CI), were calculated for all parameters.

Results

The mean age was 28.87 ± 7.19 (SD) years (range: 18-45). In all, 46 patients were eligible for analysis, with a median follow-up of 26.6 months. The baseline characters (age, stage, PS, histology, and serum markers) were not different in the two treatment arms and are represented in the [Table - 1]. The response rates and the toxicity and the cost-effectiveness analysis in both the arms are presented in [Table - 2],[Table - 3],[Table - 4], respectively.

Discussion

It has been proven in previous trials that there is no survival advantage gained by using VIP in place of the BEP in patients with high-risk germ cell tumors. [1],[4],[5] In one of the recently conducted MRC/EORTC trials, recruiting 380 patients, wherein BOP followed by VIP was compared to conventional BEP, the toxicity of the experimental arm was substantial, without providing any survival advantage. [4] In the EORTC trail comparing modified BEP with VIP, where 84 patients were studied, there is no difference in efficacy between the two regimens (CR: BEP 82% vs VIP 78%). However, grade 3/4 toxicities were more in those receiving VIP. [6] The results of the present study are not very different from other literature reports and reinforce the same. Though the CR rate is apparently higher with VIP, due to our small sample size we are not able to draw any conclusion regarding efficacy. On the whole, the recently reported trials in advanced poor-risk GCT suggest that a therapeutic plateau has been reached and it is unlikely that reconfiguration of currently available drugs will be able to improve outcomes. [5]

However we found that patients receiving VIP chemotherapy required less hospital stay than the patients receiving the BEP (30 vs 35 days; P =0.05). This is despite the fact that patients receiving VIP experience more episodes of grade 3 or 4 toxicities. The reason for this could be that patients require admission for a minimum of 7 days per course of BEP chemotherapy (admission is mandatory in most cases, even for giving bleomycin) compared to 5 days per cycle for VIP. The patients receiving BEP also required more number of hospital visits, requiring long travel and stay, compared to patients receiving VIP. Despite the cost involved in travel and the longer hospital stay, the cost of the therapy in the VIP group is significantly higher ( P =0.0001), owing to the higher cost of the drugs and the greater number of complications.

It is also important to consider another fact: most of the patients in this group will have a relapse and we need to have an effective salvage treatment available. Current literature suggests that ifosfamide is one of the most promising single chemotherapeutic agent in relapsed cases of GCT [7] and, therefore, it would be wise to keep this agent as a reserve; especially so since there is no survival advantage when it is used as a first-line agent.

In view of the absence of any survival advantage with VIP, and also because of the greater amount of toxicity and cost of therapy, it would be appropriate to treat patients of high-risk germ cell tumors with the conventional BEP rather than VIP in the Indian setting, keeping the latter regimen in reserve for the treatment of relapses.

References

1.Kaye SB, Mead GM, Fossa S, Cullen M, deWit R, Bodrogi I, et al . Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic non-seminomatous germ cell tumor: A Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study. J Clin Oncol 1998;16:692-701.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Nichols CR, Williams SD, Loehrer PJ, Greco FA, Crawford ED, Weetlaufer J, et al . Randomized study of cisplatin dose intensity in poor-risk germ cell tumors: A Southeastern Cancer Study Group and Southwest Oncology Group protocol. J Clin Oncol 1991;9:1163-72.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Chevreau C, Droz JP, Pico JL, Biron P, Kerbrat P, Cure H, et al . Early intensified chemotherapy with autologous bone marrow transplantation in first line treatment of poor risk non-seminomatous germ cell tumours: Preliminary results of a French randomized trial. Eur Urol 1993;23:213-8.  Back to cited text no. 3  [PUBMED]  
4.Kaye S, Mead G, Fossa M. An MRC/EORTC randomized trial in poor risk metastatic teratoma comparing BEP to BOP-VIP. Proc Am Soc Oncol 1995;14:246.  Back to cited text no. 4    
5.Nichols CR, Catalano PJ, Crawford ED, Vogelzang NJ, Einhorn LH, Loehrer PJ. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: An Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol 1998;16:1287-93.   Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Stoter G, Sleijfer D, Schrnagel J. BEP versus VIP in intermediate risk patients with disseminated non-seminomatous testicular cancer. Proc Am Soc Oncol 1993;12:232.  Back to cited text no. 6    
7.Wheeler BM, Loehrer PJ, Williams SD, Einhorn LH. Ifosfamide in refractory male germ cell tumors. J Clin Oncol 1986;4:28-34.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]

Copyright 2007 - Journal of Cancer Research and Therapeutics

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