Background: ModraDoc001 is a novel oral formulation containing docetaxel as a solid dispersion. Oral administration of docetaxel is feasible in combination with the CYP3A4 inhibitor ritonavir. Objectives were to determine the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of weekly oral docetaxel (as ModraDoc001) in combination with ritonavir. Methods: Patients with advanced solid tumors, WHO PS ≤ 2, no concomitant use of MDR or CYP3A modulating drugs, adequate bone marrow (ANC ≥ 1.5x10⁹ /L), liver (bilirubin ≤ 1.5xULN, ALAT/ASAT ≤ 2.5xULN) and renal function (creatinine ≤ 1.5xULN or clearance ≥ 50 ml/min) were eligible. Docetaxel (ModraDoc001 10mg capsule) and ritonavir (Norvir 100mg) were simultaneously given once weekly in a ‘3+3 cohort’ dose escalation design. MTD was defined as the highest dose resulting in <1/6 probability of causing a dose limiting toxicity in the first 4 weeks of treatment. This cohort was expanded with 6 patients. PK was determined on days 1 and 8. Results: 40 patients (25 male, 35 evaluable for safety) were enrolled in 6 dose levels (30/100, 40/100, 60/100, 80/100, 60/200 and 80/200 mg docetaxel/ritonavir). Common treatment related adverse events in the 4 highest dose levels were diarrhea (68%), nausea (62%) and fatigue (62%), mostly CTC grade 1-2 (80%, 95% and 73% respectively). Five patients experienced a DLT (grade 3 diarrhea (4), elevated ASAT/ALAT (1), grade 4 dehydration and grade 3 mucositis (1), grade 3 fatigue (2)). The MTD was 60 mg/200 mg docetaxel/ritonavir. Partial remission was seen in 4 patients (CUP, NSCLC, gastric and mamma ca) and sustained stable disease in 15 patients (6x NSCLC). Both drugs were rapidly absorbed after oral administration. Mean Tmax was 2.0 hours (CV=73%) for docetaxel. Cmax and AUC of docetaxel increased less than proportionally with dose to 162 ng/ml (CV= 67%) and 1615 ng/ml*hr (CV= 81%), respectively, in 15 patients at the MTD. Conclusions: At the MTD (once weekly 60 mg docetaxel and 200 mg ritonavir) ModraDoc001 is safe, well tolerated and shows encouraging antitumor activity. The exposure of docetaxel with this regimen is comparable to weekly intravenous administration of 35 mg/m² docetaxel. Phase II studies in solid tumors are planned.