Table 9.
Summary table for IV clinical studies with DAS (anguidine) as an anticancer agent
| Ref | Phase | Organ cancer | Dose mg/m2 per day | Dosea μg/kg bw per day | Duration/intervals days | Route | No. patients treated (no. patient evaluated for toxicity) | Adverse effects |
|---|---|---|---|---|---|---|---|---|
| Goodwin et al. (1978) | I | Advanced malignancies resistant to conventional therapeutic modalities | From 0.2 up to 6 [dose escalation] | From 5.4 up to 162 | Daily for 5 days (one month interval) |
i.v. From bolus up to 8 h infusion |
36 (24) |
Dose ≤ 2.4 nausea, vomiting Dose ≥ 2.4 neurotoxicity, GI toxicity, cardiotoxicity Myelotoxicity (inacceptable for highest dose) |
| Murphy et al. (1978) | I | Advanced malignancies |
From 0.1 and then 0.4 0.6–1 1.2–2.4 3–7.5 [dose Escalation] |
From 2.7 then 11 16–27 32–64 81–203 |
Daily for 5 days at 2‐week intervals |
i.v. 30–60 min Infusion |
39 (33) | Dose ≥ 3, nausea, vomiting, hypotension, central nervous system symptoms (including somnolence, confusion, and ataxia), diarrhoea, chills and fever, generalised burning erythema, stomatitis, shortness of breath, moderate myelosuppression |
| Belt et al. (1979) | I | Advanced malignancies resistant to conventional therapeutic modalities | 2, 3.5, 4, 6, 6.5, 10 Weekly infusion | 54, 94, 108, 162, 175, 270 | Until 36 weeks (5 patients) |
i.v. 4–8 h Infusion |
20 | Dose ≥ 2 gastrointestinal and neurologic toxic effects. Thrombocytopenia at lowest doses (2–3.5) |
| DeSimone et al. (1979) | I |
From 1.5, then 3, 5, 7.5 Weekly infusion |
From 40 then 81, 135, 203 | Repeated for 3–6 weeks |
i.v. 3 h Infusion |
29 (23) | Dose ≥ 3 Nausea and vomiting, hypotension, CNS symptoms (confusion, hallucinations, and psychomotor seizures), chills, fever, and diarrhoea | |
| Diggs et al. (1978) | II | Metastatic Adenocarcinoma colon rectum | 3.5 – liver injuries – or 5 | 94, 135 |
Daily for 5 days at 3‐week intervals |
i.v. 2–3 h infusion |
19 |
Hypotension (acute) Nausea and vomiting tolerable Myelosuppression moderate Fever and chills |
| Yap et al. (1979) | II | Advanced Breast cancer | 3 or 5 mg/m2 | 81, 135 | Daily for 5 days |
i.v. No details available |
30 (25) | Nausea and vomiting, hypotension, CNS symptoms (confusion, hallucinations, and psychomotor seizures), chills, fever, and diarrhoea |
| Bukowski et al. (1982) | II | Colon carcinoma, pancreatic, gastric cancer, miscellaneous | 3.0, 4.5 mg/m2 daily × 5‐day (dose escalation) | 81,121 | Daily for 5 days every 28 days |
i.v. 4‐h infusion |
134 (93) | Thrombocytopenia (19.8%), leucopenia (18.8%), nausea and vomiting (49%), hypotension (37%) confusion (12%) |
| Thigpen et al. (1981) | II | Sarcoma | 4.5 mg/m2 per day | 121 | Daily for 5 days every 21 days. | i.v. 4‐h infusion | 27 (25) | Myelotoxicity, nausea and vomiting, mild to moderate hypotension |
| Goodwin et al. (1983) | II | Nervous system tumour | 3.5–5 mg/m2 Weekly infusion | 94, 135 | with schedule |
i.v. 4‐h infusion |
17 (16) | myelosuppression, gastrointestinal symptoms, and central nervous system symptoms |
| Adler et al. (1984) | II | 7 different types | 3–5 mg/m2 | 94, 135 | 4‐ or 5‐day continuous infusion every 28 days | i.v. Continuous infusion | 276 (177) | Myelotoxicity |
| DeSimone et al. (1986) | II | Colorectal adenocarcinomas | 5 mg/m2 daily x | 135 | Daily for 5 days every 21 days. |
i.v 3–6 h infusion |
33 (29) | Hypotension (7/29), fever (7/29), CNS(3/29), myelotoxicity (3/29) |
bw: body weight; i.v.: intravenous.
Transformation factor of 37 (FDA, 2005) to convert the dose from m2 to kg bw.