Chemo combinatie van cisplatin en oraal etoposide voor eierstokkanker zou betere resultaten geven aldus Nederlandse onderzoekers

7 november 2012: lees vooral ook dit artikel: chemotherapie specifiek gericht op bepaalde receptoren van hormoonbepaalde vormen van kanker lijkt efficiënt en geeft hoop voor vooral gynaecologische vormen van kanker waaronder eierstokkanker, maar ook voor borstkanker, vormen van kanker - uitzaaiïngen in de buikholte ontstaan vanuit endometriose en zelfs prostaatkanker.

5 augustus 2012: Ondanks de resultaten uit onderstaande studie lijken andere meer recente studies te bewijzen dat chemo bij eierstokkanker nou niet bepaald een echt goede oplossing is. Maar hieronder het abstract van het studieverslag zoals destijds gepubliceerd in The British Journal of Cancer (British Journal of Cancer (2002) 86, 19-25. DOI: 10.1038/sj/bjc/6600002) van de studie naar een combinatie therapie van cisplatin en etoposide in de Daniel den Hoed Kliniek in Rotterdam met hoopvolle en verrassende resultaten. Ik moet er wel bij zeggen dat de onderzoekers zeggen dat de bijwerkingen meevielen, maar als je het lijstje bekijkt is dat toch nog heel indrukwekkend. Je kunt je afvragen of en hoe die bijwerkingen verminderd kunnen worden. Zie pagina onderzoek en voeding voor een schema van effecten van bepaalde vitamines bij chemo. Is wellicht interessant mee te nemen in uw beslissing dit wel of niet te doen.

d.d. 3 januari 2005: tot voor kort kon het volledige studieverslag worden ingezien bij Nature maar alles is weggehaald of geblokkeerd. Wij hebben dan ook de link weggehaald. Voor meer informatie over deze behandeling neem contact op met dr. de Wit in Erasmus Rotterdam. Zijn e-mailadres staat verderop hieronder.

De combinatie behandeling bestond uit het volgende:

Treatment

The treatment regimen consisted of 6 weekly i.v. cisplatin infusions 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 the sixth cisplatin administration continued treatment with oral etoposide 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 prehydration with 1000 ml dextrose-saline with 20 mmol KCl and 2 g MgSO4. After the cisplatin infusion the patients received posthydration consisting of 2 liters dextrose-saline with 40 mmol KCl and 4 g MgSO4 given over 8 h. All patients received ondansetron 8 mg and dexamethasone 10 mg i.v. 30 min before the start of cisplatin.

Dose reductions

Weekly cisplatin and daily etoposide: If on day 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 3.

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 was discontinued.

En de respons en resultaten zijn zo samengevat:

Response and survival

At the time of completion of the weekly cisplatin and daily etoposide 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 24 PR in the 38 platinum-sensitive patients (76%). Of the 38 platinum-sensitive patients, 14 underwent interval surgery, which confirmed four CR, one clinical CR patient had minimal residual disease, and in four patients with a PR residual tumour was debulked to less than 1 cm.

During and at the time of completion of daily etoposide maintenance therapy in responding and stable disease (SD) patients, several PR's 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 daily etoposide and continued treatment with daily oral etoposide 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 of 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 of 32 (31%), compared with that observed in the sensitive group. Also, the median response duration of 9 months, the median PFS of 8 months and the median OS of 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 cisplatin plus daily etoposide reinduction therapy and daily oral etoposide maintenance therapy, 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 of zero was 12 and 23 months, respectively, vs 7 and 13 months, respectively, in patients with WHO performance status 1-2. In patients with tumour lesions less than 5 cm the median PFS and OS was 14 and 25 months, respectively, vs 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-based chemotherapy, 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).

Verder onder dit studieverslag een kort persbericht van Dr. de Wit n.a.v. de vele vragen die hij afgelopen dagen kreeg.

Bron: British journal of cancer

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

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

1Department of Medical Oncology, Rotterdam Cancer Institute and University Hospital, 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, E-mail: wit@ouch.aze.nl

Abstract

We investigated the potential of weekly cisplatin and daily oral etoposide followed by oral etoposide maintenance therapy in patients with platinum-refractory ovarium 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 weekly for six administrations plus oral etoposide 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 evaluable patients. All 107 patients were considered evaluable for toxicity. 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 of 4-12 months, 91% responded, with 31% complete responses, a median progression-free interval of 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 of 5 and an overall survival of 13 months. Haematologic and non-haematologic, particularly renal toxicity and neurotoxicity, were notably mild. We conclude that this intensive regimen of weekly cisplatin plus daily etoposide is highly effective and well tolerated in patients with ovarian cancer relapsing after conventional platinum-based combination chemotherapy, including patients who have progressed during or within 4 months after platinum treatment.

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

Geachte mevrouw / mijnheer,

Dank u voor uw brief naar aanleiding van ons onderzoek.

Onze studie bij patiënten met eierstokkanker toonde dat kort op elkaar toegediende chemotherapie kuren, in het bijzonder de toediening van cisplatin in een wekelijks schema, effectief was bij een aanzienlijk percentage patiënten, die eerder waren behandeld met hetzelfde soort chemotherapie (cisplatin, dan wel carboplatin) elke 3 weken.

Zonder gedetailleerde informatie, meer gedetailleerd dan nu door u kan worden verstrekt, is het moeilijk, zo niet onmogelijk voor ons om te beslissen of deze therapie gunstig zou kunnen uitwerken in uw specifieke geval.
Wij raden u daarom aan ons onderzoek, dat is verschenen in het "British Journal of Cancer", januari 2002 nummer, met uw eigen arts te bespreken. Hij / zij zal, samen met u, kunnen bepalen óf onze studie resultaten een realistische behandelingsmogelijkheid voor u zou kunnen betekenen.

Met vriendelijke groeten,

Dr. R. de Wit
Internist Oncoloog

Zie ook onder nieuwsbutton op website van interne oncologie van het AZR voor meer informatie

eotposide, eierstokkanker, chemo, cisplatin