Randomised study of two doses of cisplatin with cyclophosphamide in epithelial ovarian cancer

Summary Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-'. This dose could be escalated without major toxicity to 70 mg m-2 week-'. At a dose of 80 mg m -2 myelosuppression grade 3 occurred as well as grade I nephro-and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m -2 the optimal dose intensity was reached. This schedule will be tested further in phase 11 studies.

Section: Resultsmentioning

confidence: 99%

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours

Planting¹,

Burg²,

Boer-Dennert³

et al. 1993

“…Studies indicate that approximately 20 -50% of cancer patients undergoing chemotherapy will require blood transfusions for anaemia (Skillings et al, 1993;Manegold, 1998). This percentage may be markedly increased with dose intensification and multiple cycles of chemotherapy (Groopman and Itri, 1999) such that, in those treated with platinum-based regimens, the frequency of transfusion requirements can reach 100% (Kaye et al, 1992;Nowrousian, 1998). The clinical manifestations of anaemia, such as fatigue, vertigo, dyspnoea, loss of appetite, inability to concentrate and cardiovascular problems, impair patients' functional status and sense of well-being.…”

mentioning

confidence: 99%

Impact of epoetin β on quality of life in patients with malignant disease

Boogaerts¹,

Coiffier

Kainz³

2003

117

114

This open-label, prospective study was conducted to compare the impact of epoetin b vs standard care on quality of life (QoL) in anaemic patients with lymphoid or solid tumour malignancies. A total of 262 anaemic patients (haemoglobin [Hb]p11 g dl À1 ) were randomised to a 12-week treatment with s.c. epoetin b (initial dose 150 IU kg À1 three times weekly) or standard care. Transfusions were recommended for both groups at an Hb threshold of 8.5 g dl À1 . The primary efficacy variables were improvement in QoL as measured using the Short-Form-36 physical component summary (SF-36 PCS) score and the Functional Assessment of Cancer Therapy fatigue and anaemia subscales (FACT-F and FACT-An). A visual analogue scale (VAS) was also used as a global QoL measure. Clinical response was defined as a X2 g dl À1 increase in Hb level without need of transfusion after the initial 4 weeks of treatment. Baseline to final visit changes in SF-36 PCS, FACT-F and VAS scores were significantly greater with epoetin b than with standard care (Po0.05); changes in FACT-An subscale score tended to be greater with epoetin b (P ¼ 0.076). Epoetin b significantly increased Hb concentrations relative to standard care (responders: 47% vs 13%; Po0.001). Levels of endogenous erythropoietin o50 mIU ml À1 were significantly predictive of response (OR 2.496, 95% CI: 1.21 -5.13). Epoetin b therapy significantly improves QoL compared with standard care in anaemic patients with solid tumours and lymphoid malignancies.

“…In patients with ovarian cancer, cisplatin and carboplatin demonstrated dose-related activity (Ozols et al, 1985;1987) and in these patients both probability of response and survival are directly related to dose intensity of these compounds (Levin & Hryniuk, 1987;Kaye et al, 1992). In small cell lung cancer (SCLC) the clinical outcome may also correlate with dose-intensity (Murray, 1987).…”

mentioning

confidence: 99%

Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Dercksen

Hoekman²,

Huinink³

et al. 1993

Self Cite

Summary Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression.Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 fig/kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatment differed.Constitutional symptoms were the major toxicity and in addition to the carboplatin-induced nausea and vomiting the combination was poorly tolerated. In 5/15 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x ), hypotension, severe malaise and bone pain. In this study, rhIL-3 ameliorated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhlL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferentiated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 pg/kg/d). In this study, toxicity of the treatment was mild, however, no beneficial haematologic effects of rhIL-3 could be demonstrated.In conclusion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatment (in relation to the expected nadir). In general rhIL-3-induced toxicity was mild, but combination with high dose carboplatin could be hazardous if rhIL-3 is initiated at 24 h after the cytostatic agent.