Table 1.
Summary of Primary Studies Currently Reviewed.
| Tumor Type | Species | Treatment | Results | |
|---|---|---|---|---|
| Chrono-Chemotherapy | Brain metastases of breast cancer [57] | Mice | 13 mg/kg of paclitaxel at ZT0 or ZT17 | Mice treated at ZT17 demonstrated a significant delay of neurological symptoms compared to those treated at ZT0 |
| Ovarian Cancer [53] | Human | 60 mg/m2 of Adriamycin from 0600–0630 h and 60 mg/m2 cisplatin from 1800–1830 h (schedule A) or vise versa (schedule B) | Patients on schedule B required more dose reductions and experienced more complications (i.e., infections and bleeding) | |
| Various solid tumors [49] | Human | Capecitabine every day with administration of 750 mg/m2 at 0900 h and 1250 mg/m2 at 2400 h | Maximum tolerated dose was 20% higher than that of the current approved regimen (1250 mg/m2 bi-daily) | |
| Chrono-Radiotherapy | Nasopharyngeal carcinoma [50] | Human | 80 mg/m2 of cisplatin from 1000–2200 h; 1000 mg/m2 of 5-FU and 200 mg/m2 of citrovorum factor from 2200–1000 h for 3 days | Chronomodulation of treatment significantly reduced leukocytopenia, thrombocytopenia, and nausea/vomiting when compared to constant administration |
| Nasopharyngeal carcinoma [51] | Human | DDP administration from 1000–2200 h; 5-FU administration from 2200–1000 h | Significant decrease in stomatitis during radiotherapy compared to constant administration | |
| Leukemia [29] | Mouse | 240 mg/kg of Ara-C with higher doses earlier on that the standard regimen | Increased tolerance and survival | |
| Glasgow osteosarcoma [33] | Mouse | 200 mg/kg of gemcitabine at HALO 11 or 23; 5 mg/kg of cisplatin 1 min or 4 h after gemcitabine | Decreased neutropenia and weight loss when gemcitabine given at HALO 11 regardless of cisplatin administration time | |
| Advanced non-small cell lung cancer [54] | Human | 75 mg/m2 of docetaxel on day 1; 20 mg/m2 of cisplatin on days 1–4 at either 0600 h or 1800 h; 1000 mg/m2 of gemcitabine on days 1 and 8 | Significantly reduced nausea and neutropenia with cisplatin administration at 1800 h | |
| Various metastases [55] | Human | Constant administration of FUDR with maximal flow rate in the late afternoon and minimal flow rate in the early morning | Patients receiving chronomodulated treatment experienced less severe gastrointestinal side effects and higher drug tolerance | |
| Triple negative mammary carcinoma [25] | Mouse | 5 mg/kg of cisplatin at ZT10 or ZT22 | Treatment at ZT22 reduced tumor growth, but this effect was negated by phase shift (jet lag) | |
| Glioblastoma [60] | Human | Temozolomide in the morning or evening | Patients taking Temozolomide in the morning had a higher rate of overall survival at ~5 years post-treatment | |
| Lung cancer [61] | Mouse | Novel nanoparticle-conjugated paclitaxel | Nanoparticle delivery resulted in significantly higher anti-tumor efficacy at HALO 15 than paclitaxel alone | |
| Mixed; 80% glioblastoma [66] | Human | Radiotherapy in the morning or evening | Time of day had no effect on toxicity, progression-free survival, or overall survival | |
| Rectal cancer [67] | Human | Radiotherapy in the morning or evening | Patients receiving treatment after 1200 h the majority of the time were significantly more likely to respond to treatment | |
| Naïve [69] | Rabbit | 25 mg of Sunitinib at 0800 h or 2000 h | Pharmacokinetics of the drug were significantly enhanced at 2000 h | |
| Metastatic renal cell carcinoma [70] | Human | 37.5 mg/day of sunitinib in the morning or evening | Time of day had no significant effect on efficacy, tolerance, or quality of life | |
| Imatinib-resistant/intolerant Gastrointestinal stromal tumor [71] | Human | 37.5 mg/day of sunitinib in the morning or evening | Time of day had no significant effect on efficacy or adverse events | |
| Additional Chronotherapies | Lewis lung carcinoma and sarcoma 180 [74] | Mouse | Photodynamic therapy (laser irradiation) at 0200 h or 1400 h | Tumor growth was significantly inhibited when treated during the day rather than at night |
| Melanoma [75] | Mouse | Anti-tumor vaccine at ZT9 or ZT21 | Tumor volume was significantly smaller following treatment in mice vaccinated at ZT9 rather than ZT21 | |
| Non-small cell lung cancer [79] | Human | Single-agent anti-PD-1 before or after 1630 h | Patients receiving treatment after 1630 h at least 20% of the time had a significantly shorter progression-free survival than those receiving treatment after 1630 h less than 20% of the time | |
| Stage IV melanoma [80] | Human | Ipilimumab, nivolumab, pembrolizumab, or any combo of these before or after 1630 h | Patients receiving treatment after 1630 h at least 20% of the time had a significantly shorter overall survival than those receiving treatment after 1630 h less than 20% of the time |