Chemo: Dutch researchers find new successful treatment with cisplatin and oral etoposide combination chemotherapy for ovarian cancer article update 29 december 2011.

the abstract of the study report Below dated as published in The British Journal of Cancer (British Journal of Cancer (2002) 86, 19-25. DOI: 10.1038/sj/bjc/6600002) of the study of a combination therapy of cisplatin and the Daniel den Hoed clinic in etoposide in Rotterdam with hopeful and surprising results. I must add that the researchers say that the side effects, but if you look at the list meevielen that is still very impressive. You may ask whether and how that side effects can be reduced be. See page research and nutrition for a schedule of effects of certain vitamins at chemo. Might be interesting to carry this in your decision whether or not to do.

Letter of 3 January 2005: until recently the full study report could be viewed at Nature but everything has been removed or blocked. We have therefore removed the link. For more information about this treatment please contact Dr. white in Erasmus Rotterdam. His e-mail address is later below.

The combination treatment consisted of the following:

Treatment

The treatment regimen consisted of 6 weekly i.v. infusions cisplatin on day 1, 8, 15 and day 29, 36, 43, combined with daily oral etoposide 50 mg on days 1-15 and days 29-43. The cisplatin dose was 50 mg m-2 in the platinum-sensitive patients, and later during the conduct of the study 70 mg m-2 in the intermediate-sensitive and-refractory patients. Patients with a response or stable disease after cisplatin administration continued treatment with oral etoposide in the sixth 50 mg m-2 per day for 21 days, every 4 weeks, for 6-9 cycles.

Cisplatin was dissolved in 250 ml NaCl 3% and administered over 3 h. The cisplatin infusion started after 1000 ml dextrose saline prehydration with-20 mmol KCl and 2 g MgSO4 with. After the cisplatin infusion the patients received posthydration consisting of 2 liters of saline with 40 mmol KCl and dextrose-4 g MgSO4 given about 8 h. All patients received ondansetron 8 mg and 10 mg i.v. 30 min before the start dexamethasone or cisplatin.

Dose reductions

Cisplatin and etoposide: If on day Weekly daily 8 or day 36 WBC was<2.5´109 l-1="" and/or="" platelets=""><75´109 l-1,="" treatment="" was="" postponed="" 1="" week="" until="" recovery.="" if="" on="" day="" 15="" or="" 43="" wbc="" was=""><1.5´109 l-1="" and/or="" platelets=""><50´109 l-1="" the="" cisplatin="" infusion="" was="" omitted.="" if="" on="" day="" 29="" wbc="" was=""><3.0´109 l-1="" and/or="" platelets=""><100´109 l-1,="" the="" treatment="" was="" postponed="" 1="" week="" until="" recovery.="" cisplatin="" administration="" was="" ceased="" in="" case="" the="" creatinine="" clearance="" fell="" below="" 45="" ml="" min-1="" or="" in="" case="" of="" neurotoxicity="" grade="">

Etoposide monotherapy

If WBC was<3.0´109 l-1="" and/or="" platelets=""><100´109 l-1="" on="" day="" 1,="" the="" treatment="" was="" postponed="" 1="" week="" until="" recovery.="" if="" on="" day="" 8="" or="" day="" 15="" wbc="" was=""><2.0´109 l-1="" and/or="" platelets=""><50´109 l-1, the cycle l-1,="" the="" cycle="">was discontinued.

And the response and results are so summarized:

Response and survival

At the time of completion of the weekly cisplatin and etoposide daily there were four complete responses (CR) and seven partial responses (PR) in the 28 platinum-refractory patients (39%), three CR and 26 PR in the 32 intermediate-sensitive patients (91%), and five CR and PR in the platinum-sensitive patients 24 38 (76%). Of the 38 platinum-sensitive patients, 14 underwent surgery, which confirmed four CR interval, one patient had minimal residual disease, and clinical CR in four patients with a PR residual tumour was debulked to less than 1 cm.

During and at the time of completion of daily maintenance therapy in etoposide and stable disease (SD) patients, responding several Prs converted into CR and SD into PR. The overall response to the protocol treatment is shown in Table 3. The overall response rate to weekly cisplatin plus etoposide and continued treatment with daily oral etoposide daily was as high as 92% in platinum-sensitive patients, 91% in intermediate-sensitive patients, and 46% in refractory patients.

Within the group of patients with platinum-sensitive tumours who had a 92% overall response rate, 24 or 38 (63%) of patients obtained a CR. The median response duration in this group was 14 months, the median PFS was 14 months and the median OS was 26 months. Although the 32 patients in the intermediate group also had a high overall response rate of 91%, the CR rate was lower, 10 or 32 (31%), compared with that observed in the sensitive group. Also, the median response duration of 9 months, the median PFS or 8 months and the median OS or 16 months were less than were observed in the sensitive group. Of the 28 patients who were considered cisplatin-refractory, 13 (46%) still responsed to weekly therapy and cisplatin plus daily daily oral etoposide, etoposide maintenance therapy reinduction eight of whom (29%) obtained a CR. The median response duration in the refractory patient group was 7 months, the median PFS was 5 months, and the median OS was 13 months. Response durations, PFS and OS in the three groups are shown in Table 3. Figures 1 and 2 show the curves for PFS and OS in the three groups.

Prognostic factors

The median PFS and OS in patients with a WHO performance was 12 and 23 months, respectively, or zero, US 7 and 13 months, respectively, in patients with WHO performance status 1-2. In patients with tumour lesions less than 5 cm in the median PFS and OS was 14 and 25 months, respectively, US 6 and 13 months, respectively, in patients with larger lesions.

In the univariate analysis, progression-free interval (PFI) since the last platinum-based chemotherapy, performance status and tumour size were significant prognostic factors both for PFS and OS (Table 4). In the Cox regression analysis, PFI since the last platinum-basedchemotherapy, performance status and tumour size were statistically significant prognostic factors for both the OS and PFS, except for tumour size, which did not reach statistical significance for PFS (Table 4).

Advance under this study report a short press release from Dr. de Wit based on the many questions which he received in recent days.

Source: British journal of cancer

Clinical
Weekly and daily oral etoposide is highly effective in cisplatin platinum pretreated ovarian cancer

M E L van der Burg1, the R, W L J of Putten3, A Wit1 Logmans2, W H J Stoter1 Verweij1 Kruit1, G and J

1Department of Medical Oncology, Cancer Institute and University Hospital Rotterdam, Rotterdam, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands

2Department of Gynecology, Rotterdam Cancer Institute and University Hospital, 3008 AE Rotterdam, The Netherlands

3Biostatistics, Rotterdam Cancer Institute and University Hospital, 3008 AE Rotterdam, The Netherlands


Correspondence to: Dr R de Wit, email: wit@ouch.aze.nl


Abstract

We investigated the potential of cisplatin and etoposide followed by oral weekly daily oral etoposide maintenance therapy in patients with platinum-refractory ovarian cancer. One hundred and seven patients were entered on the study, 98 patients completed the induction therapy consisting of cisplatin at either 50 or 70 mg m-2 plus oral etoposide weekly for six administrations at a dose of 50 mg daily. Of these 98 patients, 38 had a platinum treatment-free interval of more than 12 months, 32 had an interval between 4 and 12 months, and 28 had progressed during or within 4 months after last platinum therapy. We assessed response rates and time to progression, and also response duration and survival. Analyses were done on the 98 patients evaluable. All 107 patients were evaluable for toxicity considered. Of the 38 patients with a treatment-free interval of more than 12 months, 92% responded, with 63% complete responses. The median progression-free survival in these patients was 14 months, and the median survival was 26 months. Of the 32 patients with an interval or 4-12 months, 91% responded, with 31% complete responses, a median progression-free interval or 8 and a median overall survival of 16 months. Of the 28 patients with platinum-refractory disease, 46% as yet responded, with 29% complete responses, median progression-free interval or 5 and an overall survival or 13 months. Haematologic and non-renal toxicity and neurotoxicity haematologic, particularly, were notably mild. We conclude that this intensive regimen cisplatin plus daily or weekly is highly effective and well tolerated etoposide in patients with ovarian cancer relapsing after conventional platinum-based chemotherapy combination, including patients who have progressed during or within 4 months after platinumtreatment.

British Journal of Cancer (2002) 86, 19-25. DOI: 10.1038/sj/bjc/6600002

Dear Madam/Sir,

Thank you for your letter in response to our survey.

Our study showed that in patients with ovarian cancer chemotherapy administered together briefly on cures, in particular the administration of cisplatin in a weekly schedule, effective was at a significant percentage patients, who were previously treated with the same kind of chemotherapy (cisplatin or carboplatin) every 3 weeks.

Without detailed information, provided by you can be more detailed than now, it is difficult, if not impossible for us to decide whether this therapy beneficial in your specific case could elaborate.
Therefore, we strongly advise you to our research, which is published in the "British Journal of Cancer", January 2002 issue, with your own doctor to discuss. He/she will be able to determine, together with you, or our study results could mean a realistic treatment option for you.

With friendly greetings,

Dr. r. de Wit
Internist Oncologist

See also under News button on website of internal Oncology for more of the AZRinformation