Table 1.
(A) Published studies of metronomic maintenance; (B) ongoing clinical trials.
| Disease | Number of patients | Regimen used | Outcome | Toxicity | Reference |
|---|---|---|---|---|---|
| (A) | |||||
| NSCLLC | 65 Maintenance 65 Observation | Paclitaxel 70 mg/m2 weekly 3 out of 4 weeks | PFS 38 vs. 29 weeks OS 75 vs. 60 weeks | One grade 3 or 4 toxicity – 45% | (35) |
| NSCLC | 141 Received maintenance | Paclitaxel 70 mg/m2 weekly 3 out of 4 weeks | Median, TTP 33 weeks for arm 1 and 29 weeks for arm 2 (induction regimen arms) | Grade 4 neutropenia – 2.1%; Grade 3 toxicities: anemia (0.7%), neuropathy (2.1%), arthralgia (2.1%), fatigue (2.8%), dyspnea (2.1%), and abdominal pain (2.1%) | (36) |
| Various GI cancers | 28 Patients | Capecitabine 1000 mg twice daily continuous | Efficacy not described | Only one grade 3 toxicity | (37) |
| Pediatric brain tumors (after HSCT) | 10 Patients | Alternate cycles of 21 days of etoposide 50 mg/m2, cyclophosphamide 2.5 mg/kg/day, temozolomide 90 mg/m2/day, along with alt courses of celecoxib 100 mg BD, isotretinoin 100 mg/m2/day | 8 out of 10 patients had stable disease at a mean duration of follow up of 20 months | Mild emesis (4/10), 1/10 had prolonged myelosuppression | (38) |
| Ovarian carcinoma | 64 Patients | Paclitaxel 60 mg/m2 weekly for 21 weeks | 3 year PFS 18%, 3 year OS 64% | Grade 2 neutropenia – 25.9%, Grade 2 sensorial neurotoxicity – 20.7%, Grade 2 motor neurotoxicity – 6.9% | (39) |
| Metastatic breast cancer | 15 | mC 1500 mg daily plus docetaxel 75 mg/m2 on day 1 of a 4-week cycle up to six cycles, followed by mC as maintenance | Objective response rate 41.7%, 1 (8.3%) CR, 4 (33.4%) PR, 6 (50%) SD clinical benefit of 66.7%, median time to progression 8.4 months | All toxicities occurred during D plus mC combination | (40) |
| Disease and clinical setting | Regimen | Official title | Clinical trial identifier | ||
| (B) | |||||
| Breast cancer, ER, PR negative after adjuvant chemotherapy | CMM (cyclophosphamide 50/mg/day orally continuously for 1 year; methotrexate 2.5 mg/twice a day orally days 1 and 2 of every week for 1 year) | OT2-01-01: International Breast Cancer Study Group (IBCSG) trial 22-00 | IBCSG 22-00 | ||
| Met CRC, after response to FOLFIRI + Bev | Capecitabine, celecoxib, and methotrexate | Metronomic chemotherapy with anti-angiogenic effect as maintenance treatment for metastatic colorectal carcinoma following response to FOLFIRI + bevacizumab: clinical and laboratory studies | NCT01668680 | ||
| Mets CRC after CAPOX–Bev | Capecitabine 625 mg/m2 bid daily continuously and bevacizumab 7.5 mg/kg iv q 3 weeks | Maintenance treatment with capecitabine and bevacizumab vs. observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC): the phase III CAIRO-3 study of the Dutch Colorectal Cancer Group (DCCG) | NCT00442637 | ||
| Met MBC | Capecitabine 500 mg/m2 three times daily on days 1–21 of each 3-week cycle and capecitabine 1000 mg/m2 twice daily on days 1–14 of each 3-week cycle | A randomized phase III study of metronomic vs. intermittent capecitabine maintenance therapy following first-line capecitabine and docetaxel therapy in HER2-negative metastatic breast cancer | NCT01917279 | ||
| Ovarian carcinoma, stage 3, after adjuvant chemotherapy | Cytophosphan tab 50 mg – 1 × 1 per day, continuous Celecoxib tab 200 mg – 1 × 2 per day, continuous Methotrexate tab 2.5 mg – 1 × 2 per day, 2 days weekly | Maintenance treatment for ovarian carcinoma in remission by an anti-angiogenic treatment strategy with metronomic/oral chemotherapy (cytophosphan combined with low-dose methotrexate) and COX-2 inhibition (celecoxib) | NCT01175772 | ||