Sixteen of the 64 patients (25%) required a dose reduction or discontinuation of docetaxel (Table 3). In the group that did not experience M-AS, there were nine cases (20%) that required dose reduction or discontinuation of docetaxel, with the most prominent reason being skin toxicity (including palmar–plantar syndrome), followed by fatigue, gastrointestinal toxicity, and neutropenia. In the group that experienced M-AS, there were seven cases (37%) that required a dose reduction or opted for discontinuation of docetaxel, of which in five patients (26%) these were due to the arthralgia–myalgia pain (one patient of these five had also developed febrile neutropenia) (Table 3). Patients with M-AS were significantly more likely to discontinue docetaxel treatment (four patients [21.1%] compared with two patients [4.4%] in the control group, χ2 =4.33, p=0.033).

Cycle 4 of the FEC-D protocol involves the introduction of docetaxel chemotherapy, and the M-AS group had a significantly higher mean pain at this point in their treatment (Figure 2). The mean ESAS pain score in the M-AS group was 7 with standard deviation (SD) of 2.23 vs a mean of 1.13 with SD of 1.76 in the control group (two-tailed t-test =11.2, p<0.0001).

Treatment of M-AS

Of the 19 patients who developed M-AS following docetaxel infusion, three patients were prescribed the atypical antiepileptics gabapentin (one patient) and pregabalin (two patients). The two patients treated with pregabalin (both at 25 mg three times a day) had a complete and partial response of their pain. Extended use of corticosteroids, beyond Day 2 that is the standard premedication regimen of docetaxel, was another commonly encountered M-AS therapy and was prescribed in six patients (in one patient together with opioids). It had a complete or partial effectiveness in five of the six patients. Six more patients were treated with opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or combinations thereof. The four patients who had opioids included in their treatment seemed to have a better response than the two patients treated with acetaminophen or NSAIDs (ibuprofen) alone. Four patients did not receive any specific analgesic treatment for their M-AS (three of them were given prescriptions that did not fill and the fourth did not report the syndrome and decided to discontinue further treatment).

Three patients were excluded from the group comparisons because they were chronically taking gabapentin (two patients) or pregabalin (one patient) at the time of their docetaxel treatment for other indications. No M-AS or increase of preexisting pain was documented in any of these three patients.