INTRODUCTION:

Cancer is a disease process that begins when an abnormal cell is transformed by the genetic mutation of the cellular DNA. A death from cancer worldwide is estimated to be 13.1 million in 2030 (WHO 2016). Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of many chemotherapeutic agents (Loprinzi et al 2011). A common side effect of chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). Neurotoxic chemotherapeutic agents include the taxanes (paclitaxel, docetaxel), the vinca alkaloids (vinorelbine), the platinum analogues (cisplatin, carboplatin), and the antimetabolites (capecitabine) ,most recently Thalidomide and Bortezomib has been reported to have an association with the progress of dose and treatment-limiting CIPN, by activating mitochondrial and vascular dysfunction which leads to sensory loss and reduced muscle strength, functions that depend upon cellular mitochondria to generate energy in the form of ATP (adenosine triphosphate). CIPN compromises quality of life, also affects patients activity of daily living and results in pain or discomfort (Cavaletti et al, 2002). Sensory symptoms are more common than motor or autonomic symptoms. The autonomic symptoms are cardiovascular (blood pressure oscillation), gastrointestinal (constipation) and urologic (erection problems and urinary retention) symptoms. Motor symptoms manifest as distal weakness (such as feet weakness), gait and balance disorders, and difficulties with fine movements (writing, buttoning clothes, cutting and sewing). (Grisold et al, 2012). Sensory symptoms are bilateral paresthesias, numbness and tingling in 90% of CIPN cases. The patient also report complaints of sensation of “wearing a thin sock or glove”, as well as “difficulty to hold things” and to distinguish shape, texture and/or temperature.

The combination of medical history, neurologic examination, electrodiagnostic studies, and basic laboratory testing will yield an etiologic diagnosis in 74% to 82% of patients with polyneuropathy. (England et al, 2009). CIPN is most frequently assessed using common toxicity grading scales (e.g. NCI-CTC) and quality of life by EOQRTC QLQ- 30 scale. The flexibility test by sit and reach method. The cardiorespiratory fitness Vo2 max by Uth–Sørensen–Overgaard–Pedersen ie Vo2 max=HR max/HR rest x15.3 ml /kg-minute. Clinical trials of the antiepileptic agents gabapentin (Rao et al ,2007) and lamotrigine (Rao et al, 2008) and the antidepressants nortriptylineand amitriptyline have all been negative.( Hammack, 2002).

All the drugs to treat CIPN are commonly prescribed for use in other conditions (i.e. depression, pain, muscle spasms) have some effect on reducing CIPN severity. For this reason, the researcher believes in combining complementary therapy approaches (massage and Exercise therapy) along with usual drug to hopefully get greater symptom relief. Only a few researchers have been done to see the effectiveness on CIPN in India. Hence a study is designed to determine the effectiveness of Exercises, massage therapy and knowledge teaching on Home Safety Measures among patients receiving cancer chemotherapy.

MATERIAL AND METHODS:

Participants: True experimental research design was used .one hundred and twenty cancer patients receiving cancer chemotherapy were selected by using simple random sampling method in this study. Permission was obtained from the authorities of the hospital to carry out study. The patients were randomly assigned to control and experimental group by Random table method. This study was approved by the institutional Human Ethics Committee of Saveetha University. (2017/IEC/SU; Dated 11 August 2017)

Inclusion and exclusion criteria:

Patients receiving chemotherapeutic agents which cause neurotoxic effects like taxanes (paclitaxel, docetaxel), the vinca alkaloids (vinorelbine), the platinum analogues (cisplatin, carboplatin), and the antimetabolites (capecitabine) with grade I, II, III were selected. Patients who are not able to perform basic activities of daily living such as walking and Patient with co-morbid diseases that might hamper physical exercise (e.g. heart failure, chronic obstructive pulmonary disease (COPD), orthopaedic conditions and neurological disorders like Cerebro vascular accident and diabetes mellitus were excluded.

Experimental Phase:

The recruitment process involved introduction of patient to the researcher by oncology physician. Initially 130 patients were recruited for the study from the oncology patient chemo Database registry excluding nonwillingness patients. An assessment meeting was scheduled in the hospital after the criteria were met. After all questions were answered regarding the study protocol , the patients agreed to participate in the study and signed the informed consent prior to the beginning of the administration of the assessments. The patients were allotted to the respective experimental and control group by random allocation method. However, 10 patients dropped out of the study during the course of the 12-week training program. Reasons for ceasing participation included 4 patients referred to other hospital, four patients died and two were non compliance to the treatment. Thus a total of 120 patients completed the 12-week home-based exercise program. Prior to the day of chemotherapy administration, after all the assessment criteria were completed, the demographic profiles of all patients of both Experimental and control group were obtained by the structured questionnaire, signs of CIPN by NCI-CTCAEV scale, neuropathic pain by LANSS scale, Quality of life by EOQRTC QLQ-30 scale, knowledge on home safety measures by structured questionnaire(ie pretest) and predemo of exercises were done only to the patients of Experimental group and they were asked to return demonstrate the exercises. The patients in control group followed the routine care. On the day of chemotherapy administration, the emerging signs of CIPN were observed and they were not asked to do the exercises due to the chemotherapy related fatigue. On the day after chemotherapy the patients were asked to do the exercises as demonstrated before and intervention is given in the table:1.

All the patients participated in an individualized prescriptive exercise intervention 3 to 4 times per week, depending on the physical status of each patient during each week, for a period of 12 weeks. The exercise interventions began on the next day of chemotherapy administration ie 1^st week of 1^st month. Each exercise session was administered in the morning. Patient not exercised for more than 30 minutes, had a rest period of 36 hours to recover before the next exercise bout. (i.e. If a patient exercised on Monday, the next exercise session was administered on Wednesday). If a patient reported extremely tired prior or during an exercise session, the duration of the session was significantly reduced.

The patients were discharged after the in-hospital exercise training program. During this period, subjects received an exercise prescription containing primarily cardiovascular workouts and were asked to continue exercising on a regular basis until they returned to the hospital for their second and third phase of treatment. A detailed exercise and massage log sheet is provided to each patient, whereby they can enter such information as exercise duration, steps taken, sets and reps completed, rating of perceived exertion, and the massage techniques. The patients were instructed how to fill out the activity log and was asked to give the feedback through mobile app and this provided the chance for each patient to report and track their exercise status. Participants received weekly phone calls from the research staff, where the participant’s activity was reviewed, progress was reinforced, and goals were set for the following week.

TABLE: 1 EXERCISE PROTOCOL AND CARE BUNDLE APPROACH

S.No	Exercises	Duration	Frequency	Body work outs	Intensity/RPE
1	Aerobic Exercises Cardio-Respiratory component	5 minutes	od morning	Breathing exercises	40%-60% Not more than 5 on Borg scale
2	Stretching component	3 – 5 minutes	od morning	Calf, hamstring, plantar fascia stretch	40%-60% Not more than 5 on Borg scale
3	Resistance training component	5 – 10 minutes	od Morning	Upper body workouts Scapular motion such as elevation, depression, adduction, abduction, upward and downward rotation of shoulder, abdominal crunches Lower body workouts Calf raise, chair squat, seated dorsiflexion, leg extension, leg curls. Feet exercises Tennis ball roll under the toe stretch, heel and toe raise, front foot stretch.	40%-60% Not more than 5 on Borg scale
4	Balance training exercises	5 minutes	od Morning	Bipedal ankle inversion, eversion, unipedal balance, calf raise, hip flexion, side leg raise.	40%-60% Not more than 5 on Borg scale
5	Massage therapy (Evening session)	20 minutes	od Evening	Effleurage,petrissage,tapotement,friction for hand and feet	Not more 20 minutes
6.	Health Education (Evening session)	10 minutesHandouts	od Evening	Home safety measure: House hold recommendation, Good lighting, pot holders, use caution while using sharp instruments, nonslippery floor, check the water temperature by palm of the hand, set the water temperature below 120,hand rails in stair case.	Reinforcement was given to the patients, when they came to hospital for the next consecutive cycles of chemotherapy(6weeks).

Table 2 : comparison of level of CIPN by NCI-CTCAE Scale in pretest and post tests of control and experimental groups

S.No	Parameter	Group	Median (Percentile) (25-75)	Statistical analysis
S.No	Parameter	Group	Median (Percentile) (25-75)	Statistical analysis
1	NCI CTCAE Sensory	Control pre	1.000 ( 0.250 - 2.000)	Given in figure 1a
		post test 1	1.000 ( 1.000 - 2.000)
		post test 2	1.000 ( 1.000 - 2.000)
		post test 3	1.000 ( 1.000 - 2.000)
		Experimental pre	1.000 ( 0.000 - 2.000)
		post test 1	1.000 ( 1.000 - 2.000)
		post test 2	1.000 ( 1.000 - 2.000)
		post test 3	0.000 ( 0.000 - 1.000)
2	NCI CTCAE Motor	Control pre	2.000 ( 1.000 - 2.000)	Given in figure 1b
		post test 1	1.500 ( 1.000 - 2.000)
		post test 2	1.000 (1.000 - 2.000)
		post test 3	1.000 (1.000 - 2.000)
		Experimental pre	1.000 (1.000 - 2.000 )
		post test 1	1.000 (0.000 - 2.000 )
		post test 2	1.000 (1.000 - 1.000 )
		post test 3	1.000 (0.000 - 1.000 )
3	NCI CTCAE Autonomus	Control pre	1.000 (1.000 - 2.000 )	Given in figure 1 c
		post test 1	1.000 (1.000 - 2.000 )
		post test 2	1.000 (1.000 - 2.000 )
		post test 3	1.000 (1.000 - 2.750 )
		Experimental pre	1.000 (1.000 - 2.000 )
		post test 1	1.000 (0.000 - 2.000 )
		post test 2	1.000 (1.000 - 1.000 )
		post test 3	1.000 (1.000 - 1.000 )
4	NCI CTCAE PIN	Control pre	1.000 (1.000 - 2.000 )	Given in figure 1 d
		post test 1	1.000 (1.000 - 2.000 )
		post test 2	1.000 (1.000 - 2.000 )
		post test 3	1.000 (1.000 - 2.000 )
		Experimental pre	1.000 (1.000 - 2.000 )
		post test 1	1.000 (0.000 - 2.000 )
		post test 2	1.000 (1.000 - 1.000 )
		post test 3	1.000 (0.250 - 1.000 )
5	NCI CTCAE Vibration	Control pre	1.000 (1.000 - 2.000 )	Given in figure 1 e
		post test 1	1.000 (1.000 - 2.000 )
		post test 2	1.000 (0.000 - 2.000 )
		post test 3	1.000 (0.000 - 2.000 )
		Experimental pre	1.000 (1.000 - 2.000 )
		post test 1	1.000 (0.000 - 2.000 )
		post test 2	1.000 (0.000 - 1.750 )
		post test 3	1.000 (0.000 - 1.000 )
6	NCI CTCAE Muscle strength	Control pre	1.000 (1.000 - 2.000 )	Given in figure 1 f
		post test 1	1.000 (1.000 - 2.000 )
		post test 2	1.000 (0.000 - 2.000 )
		post test 3	1.000 (1.000 - 1.750 )
		Experimental pre	1.000 (1.000 - 2.000 )
		post test 1	1.000 (0.000 - 2.000 )
		post test 2	1.000 (0.000 - 2.000 )
		post test 3	1.000 (0.000 - 1.000 )
7	NCI CTCAE Tendon reflex	Control pre	1.000 (1.000 - 2.000 )	Given in figure 1 g
		post test 1	1.000 (1.000 - 2.000 )
		post test 2	1.000 (1.000 - 2.000 )
		post test 3	1.000 (0.000 - 1.000 )
		Experimental pre	1.000 (0.000 - 2.000 )
		post test 1	1.000 (0.000 - 2.000 )
		post test 2	1.000 (0.000 - 1.750 )
		post test 3	0.000 (0.000 - 1.000 )
8	NCI CTCAE Total	Control pre	10.000 (8.000 - 13.000)	Given in figure 1 h
		post test 1	10.000 (7.250 - 13.000)
		post test 2	9.000 (4.250 - 12.750)
		post test 3	9.000 (4.000 - 13.000)
		Experimental pre	9.000 (4.250 -13.000)
		post test 1	7.000 (3.000 - 13.000)
		post test 2	6.000 (4.000 - 11.000)
		post test 3	5.000 (2.250 - 7.750)

Figure 1 h: Effectiveness of care bundle approach on CIPN-total score, of control and experimental groups.

The middle red line is median and the blue line is the mean (n = 60 each).

The c2 and P values are by Friedman RM ANOVA of the respective groups.

The control and experimental groups are compared by Mann-Whitney rank sum test.

For the Pre-test the ‘T’ and ‘P’ values are 3855 and 0.238 respectively; For the Post-test 1 the ‘T’ and ‘P’ values are 4000 and 0.050 respectively; For the Post-test 2 the ‘T’ and ‘P’ values are 4007 and 0.048 respectively; For the Post-test 3 the ‘T’ and ‘P’ values are 4270 and 0.002 respectively.

a – Significantly different from the respective Pre-test.

b – Significantly different from the respective control group.

Table 3 Comparison of quality of life by EOQRTC scale in pretest and posttest of control and Experimental groups

S.No	Parameter	Group	Median (Percentile) (25-75)	Statistical details
S.No	Parameter	Group	Median (Percentile) (25-75)	Statistical details
1	EOQRTC GLOBAL STATUS	Control pre	33.3 (10.4 -58.3)	Given in fig 2 a
		post test 1	38.5 (20.25 - 75.00)
		post test 2	40 (25 - 75.25)
		post test 3	43.5 (25.25 -70.25)
		Experimental pre	33.3 (18.77 - 66.7)
		post test 1	45.85 (33.3 -81.22)
		post test 2	75 (43.77 -89.6)
		post test 3	83.3 (52.07 - 91.7)
1	EOQRTC Physical functioning	Control pre	39.000 (20.000-72.000)	Given in fig 2 b
		post test 1	39.000 (20.000-70.000)
		post test 2	40.000 (26.175 - 72.000)
		post test 3	43.000 (24.250 - 85.750)
		Experimental pre	46.700 (20.000 - 80.000)
		post test 1	49.850 (33.300 - 80.000)
		post test 2	66.700 (33.300 - 93.300)
		post test 3	80.000 (54.975 - 93.300)
2	EOQRTC Role functioning	Control pre	33.300 (16.700 - 50.000)	Given in fig 2 c
		post test 1	39.000 (33.250 -78.000)
		post test 2	39.000 (30.000 - 80.750)
		post test 3	40.000 (30.000 - 85.000)
		Experimental pre	50.000 (20.850 - 66.700)
		post test 1	50.000 (20.850 - 83.300)
		post test 2	66.700 (33.300 - 83.300)
		post test 3	66.700 (50.000 - 95.825)
3	EOQRTC Emotional functioning	Control pre	25.000 ( 8.300 - 58.300)	Given in fig 2 d
		post test 1	37.000 (22.000 - 75.750)
		post test 2	40.000 (22.050 - 78.500)
		post test 3	44.000 (22.000 - 81.500)
		Experimental pre	41.700 (27.075 - 66.700))
		post test 1	45.850 (33.300 - 81.225)
		post test 2	75.000 (35.400 - 83.300)
		post test 3	75.000 (52.075 - 91.700)
4	EOQRTC Cognitive functioning	Control pre	33.300 (16.700 -66.700)	Given in fig 2 e
		post test 1	33.300 (33.300 - 66.700)
		post test 2	50.000 (26.000 - 82.250)
		post test 3	44.500 (18.250 - 80.000)
		Experimental pre	33.300 (16.600 - 62.525)
		post test 1	50.000 (33.300 - 66.700 )
		post test 2	66.700 (33.300 - 83.300)
		post test 3	75.000 (50.000 -100.000)
5	EOQRTC Social functioning	Control pre	33.300 (16.700 - 66.700)	Given in fig 2 f
		post test 1	33.300 (16.700 - 66.700)
		post test 2	40.000 (25.250 - 89.500)
		post test 3	50.000 (32.250 - 83.300)
		Experimental pre	16.700 (16.700 - 50.000)
		post test 1	33.300 (33.300 -66.700)
		post test 2	66.700 (33.300 - 83.300)
		post test 3	66.700 (50.000 - 100.000)
6	EOQRTC Fatigue	Control pre	88.900 (36.075 - 100.000)	Given in fig 2 g
		post test 1	88.900 (33.300 - 100.00 )
		post test 2	88.900 (22.200 - 100.000)
		post test 3	88.900 (22.200 - 88.900)
		Experimental pre	22.200 (11.100 -41.625)
		post test 1	33.300 (22.200 - 52.800)
		post test 2	44.400 (33.300 - 75.025)
		post test 3	77.800 (55.600 -88.900)
7	EOQRTC Nausea and vomiting	Control pre	33.300 (16.700 - 50.000)	Given in fig 2 h
		post test 1	33.300 (16.700 - 62.625 )
		post test 2	41.650 (33.300 - 66.700)
		post test 3	50.000 (33.300 - 79.150)
		Experimental pre	33.300 (16.700 - 50.000)
		post test 1	33.300 (33.300 - 66.700 )
		post test 2	50.000 (33.300 - 83.300)
		post test 3	75.000 (50.000 - 100.000)
8	EOQRTC Dyspnea	Control pre	36.500 (29.000 - 68.000)	Given in fig 2 i
		post test 1	39.000 (27.500 - 79.750)
		post test 2	42.500 (33.000 - 87.750 )
		post test 3	48.000 (32.000 - 87.750)
		Experimental pre	33.300 (16.700 - 50.000)
		post test 1	33.300 (33.300 - 79.150)
		post test 2	50.000 (33.300 - 83.300)
		post test 3	83.300 (50.000 - 83.300)
9	EOQRTC Insomnia	Control pre	37.000 (21.000 - 73.000 )	Given in fig 2 j
		post test 1	38.500 (27.250 - 72.000 )
		post test 2	40.000 (27.250 - 82.250)
		post test 3	40.000 (27.250 - 85.000)
		Experimental pre	25.000 (16.700 - 33.300)
		post test 1	33.300 (16.700 - 50.000)
		post test 2	66.700 (33.300 - 83.300 )
		post test 3	75.000 (50.000 - 83.300)
10	EOQRTC Appetite loss	Control pre	33.300 (16.700 - 50.000)	Given in fig 2K
		post test 1	33.300 (17.250 - 40.000)
		post test 2	40.000 (22.000 - 79.150)
		post test 3	45.000 (26.000 - 83.300)
		Experimental pre	16.700 (16.700 - 29.150)
		post test 1	33.300 (33.300 - 50.000)
		post test 2	50.000 (33.300 - 83.300)
		post test 3	83.300 (66.700 - 100.000)
11	EOQRTC Constipation	Control pre	33.300 (16.700 - 50.000 )	Given in fig 2 L
		post test 1	38.500 (30.000 - 79.750)
		post test 2	39.000 (28.500 - 81.750 )
		post test 3	52.500 (28.500 - 86.000 )
		Experimental pre	16.700 (16.700 - 50.000 )
		post test 1	33.300 (33.300 - 66.700 )
		post test 2	50.000 (33.300 - 83.300 )
		post test 3	83.300 (66.700 - 100.000 )
12	EOQRTC Diarrhoea	Control pre	25.000 (16.700 - 50.000 )	Given in fig 2 M
		post test 1	38.000 (30.000 - 78.000 )
		post test 2	37.500 (28.000 - 82.750 )
		post test 3	44.500 ( 31.500 - 87.750)
		Experimental pre	16.700 ( 16.700 - 50.000 )
		post test 1	33.300 (33.300 - 66.700 )
		post test 2	50.000 (33.300 - 83.300)
		post test 3	83.300 (50.000 - 100.000)
12	EOQRTC Financial difficulties	Control pre	22.200 ( 11.100 - 55.600 )	Given in fig 2 N
		post test 1	33.300 (22.500 - 58.250 )
		post test 2	40.000 ( 22.750 - 75.500 )
		post test 3	42.500 ( 33.075 - 78.000)
		Experimental pre	16.700 (16.700 - 50.000 )
		post test 1	33.300 (33.300 - 62.525)
		post test 2	58.350 (37.475 - 83.300 )
		post test 3	83.300 (66.700 - 83.300 )

Table 9.1(i) comaparison of control and experimental group sensory nerve conduction parameters.

S.NO	PARAMETER	GROUP	Mean	STANDARD ERROR	UNPAIRED T TEST		PAIRED TEST
S.NO	PARAMETER	GROUP	Mean	STANDARD ERROR	Con pre Exp pre	Con post Exp post	Con pre Con post	Exp pre Exp post
1	Sensory median CV	control pre	42.292	2.197
		Exp pre	44.090	0.951
		control post	42.759	2.289	t =0.751	t =1.692	t =0.157	t =2.861
		Exp post	46.843	0.764	p=0.457	p=0.099	p=0.877	p=0.010
2	Sensory median Amplitude	control pre	3.921	0.205	t =1.203	t =3.035	t =2.056	t=2.625
		Exp pre	4.625	0.549	p=0.236	p=0.099	p=0.054	p=0.004
		control post	4.479	0.468
		Exp post	9.122	1.456
3	Sensory median latency	control pre	4.708	0.225	t=0.103	t=0.033	t =2.007	t =1.45
		Exp pre	4.735	0.134	p=0.918	p=0.974	p=0.059	p=0.163
		control post	4.314	0.268
		Exp post	4.325	0.228
4	Sensory sural CV	control pre	44.001	0.841	t =1.391	t =2.790	t =0.676	t =2.656
		Exp pre	45.650	0.835	p=0.172	p=0.008	p=0.507	p=0.016
		control post	44.562	0.786
		Exp post	47.595	1.751
5	Sensory sural Amplitude	control pre	5.247	1.140	t=0.658	t =2.790	t =0.338	t =2.763
		Exp pre	4.427	0.504	p=0.514	p=0.008	p=0.739	p<0.009
		control post	4.828	0.841
		Exp post	8.386	0.975
6	Sensory sural latency	control pre	4.738	0.163	t =0.319	t =1.749	t =0.965	t =2.866
		Exp pre	4.805	0.130	p=0.752	p=0.008	p=0.347	p=0.088
		control post	5.593	0.900
		Exp post	3.916	0.333
7	Sensory Ulnar CV	control pre	44.416	0.899	t =0.529	t =2.280	t =0.495	t =1.648
		Exp pre	43.170	2.179	p=0.600	p=0.028	p=0.626	p=0.116
		control post	44.201	0.816
		Exp post	46.813	0.805
8	Sensory Ulnar Amplitude	control pre	4.840	0.828	t =0.870	t =1.332	t =0.352	t =2.610
		Exp pre	3.993	0.513	p=0.390	p=0.191	p=0.729	p=0.017
		control post	5.232	1.133
		Exp post	7.546	1.318
9	Sensory Ulnar latency	control pre	4.908	0.183	t =0.516	t =0.927	t =1.238	t =1.402
		Exp pre	4.787	0.144	p=0.609	p=0.360	p=0.231	p=0.177
		control post	4.698	0.245
		Exp post	4.405	0.201

Table:7 comparison of moor nerve conduction parameters of control and experimental group.

S.No	Parameter	Group	Mean + SE	Unpaired t test		Paired t test
				Con pre Exp pre	Con post Exp post	Con pre Con post	Exp pre Exp post
1	Motor median latency	Con pre	4.743+0.128	0.762 0.451	1.721 0.093	t=0.317 p=0.755	2.138 0.046
		Exp pre	4.877+0.121
		Con post	4.687+0.129
		Exp post	4.192+0.257
2	Motor median amplitude	Con pre	5.827+1.549	1.568 0.125	0.735 0.467	0.342 0.736	3.571 0.002
		Exp pre	3.389+0.144
		Con post	6.619 +1.528
		Exp post	8.117+1.349
3	Motor median cv	Con pre	45.166+1.301	0.845 0.403	0.448 0.656	1.048 0.308	1.945 0.067
		Exp pre	43.014+2.189
		Con post	47.515+1.555
		Exp post	46.734+0.782
4	Motor ulnar latency	Con pre	4.946+0.102	0.182 0.856	1.554 0.128	0.472 0.642	2.024 0.057
		Exp pre	4.972+0.099
		Con post	4.866+0.134
		Exp post	4.458+0.226
5	Motor ulnar amplitude	Con pre	5.174+1.229	1.524 0.136	0.307 0.760	0.565 0.578	2.737 0.013
		Exp pre	3.281+0.180
		Con post	6.346+1.525
		Exp post	6.980+1.389
6	Motor ulnar cv	Con pre	46.108+1.638	1.073 0.290	1.195 0.240	0.202 0.842	0.033 0.974
		Exp pre	44.149+0.808
		Con post	46.634+1.854
		Exp post	44.105+1.020
7	Motor peroneallatency	Con pre	4.926 0.164	0.005 0.996	2.293 0.027	0.150 0.882	2.531 0.020
		Exp pre	4.925 0.100
		Con post	4.902 0.142
		Exp post	4.165 0.288
8	Motor peroneal amplitude	Con pre	5.921 1.447	0.702 0.487	1.542 0.131	0.266 0.793	2.282 0.034
		Exp pre	4.897 0.182
		Con post	6.501 1.402
		Exp post	4.306 0.244
9	Motor peroneal cv	Con pre	45.711 1.651	0.926 0.360	0.647 0.521	1.014 0.323	2.068 0.052
		Exp pre	43.966 0.908
		Con post	47.831 1.551
		Exp post	46.694 0.822
10	Motor tibial latency	Con pre	4.943 0.112	0.061 0.951	2.164 0.037	0.718 0.481	2.417 0.026
		Exp pre	4.934 0.107
		Con post	4.849 0.100
		Exp post	4.237 0.265
11	Motor tibial amplitude	Con pre	4.452 0.614	1.257 0.217	1.951 0.058	1.187 0.250	1.293 0.211
		Exp pre	3.671 0.094
		Con post	6.457 1.533
		Exp post	3.451 0.152
12	Motor tibial cv	Con pre	45.987 1.537	0.550- 0.586	0.742 0.462	0.162 0.873	2.038 0.056
		Exp pre	45.030 0.817
		Con post	45.669 1.307
		Exp post	46.778 0.721

Table 7 illustrates The motor and sensory nerve conduction parameters in pre test and post test for control and experimental groups and analyzed by one way analysis of variance. Paired t- test was used to compare the pretest and post test of control and experimental groups.. A probability of 0.05 or less was taken as statistically significant. The analysis and plotting of graphs were carried out using sigma plot 12.(Systat Software Inc.,USA)

Motor Nerve Conduction (ulnar nerve -AMP): The Experimental group pretest score of ulnar nerve AMP was statistical significant difference in Experimental group. p=0.013.

Motor Nerve Conduction (median nerve -LT):The Experimental group pretest and posttest score was statistical significant difference in Experimental group. p=0.046.

Motor Nerve Conduction (median nerve -AMP): The Experimental group pretest score of median nerve AMP was statistical significant difference in Experimental group. p=0.002.

Motor Nerve Conduction (peroneal nerve -LT): The Experimental group pretest score peroneal nerve was statistical significant difference in Experimental group. p=0.02.The control posttest score of peroneal nerve LT was significantly different from the experimental posttest score. (p=0.027).

Motor Nerve Conduction (peroneal -AMP): The Experimental group pretest score of peroneal nerve AMP was statistical significant difference in Experimental group. p=0.034.

Motor Nerve Conduction (Tibial nerve -LT): The Experimental group pretest score of tibial nerve LT was statistical significant difference in Experimental group. p=0.026,The control posttest score of tibial nerve LT was significantly different from the experimental posttest score. (p=0.037) which showed that experimental group patients got benefitted from massage therapy, exercises and Health education on home safety measures .

Motor Nerve Conduction (Tibial nerve -AMP): The control posttest score of tibial nerve AMP was statistically significantly different from the experimental posttest score. (p=0.05) but there is improvement in lower limb numbness after the intervention.

In all the four nerves, there was a statistical significant difference was seen in the parameter Amplitude and latency among Experimental group p=0.01,which showed that there is a improvement in neuropathy after the intervention in experimental group. Also noteworthy myelination of nerve is directly proportional to the nerve impulses that reaches the determined distance at determined time(Amplitude) .This finding is consistent with the researchers finding that the significant improvement in amplitude and latency parameter signalizing the nerve regeneration.

The vo2 max parameter in pre test and post test in control and experimental groups were analyzed by one way analysis of variance .Paired t- test was used to compare the pretest and post test of control and experimental groups. A probability of 0.05 or less was taken as statistically significant. The analysis and plotting of graphs were carried out using sigma plot 12.(Systat Software Inc., USA).

Fig 5a and 5b illustrates the scores of Vo2 max :The experimental posttest 3 vo2 max score was not statistically significant from the control posttest 3 score.(t=729;p=0.469) for males but the experimental posttest 3, vo2 max score was statistically significant from the control posttest 3 score.(t=3.198;p=0.002).for females This gender difference will not influence the study results as maximal aerobic capacity and lung function will not change by either training and non training.

Fig 6a and 6b illustrates the scores of sit and reach :The sit and reach parameter in pre test and post test in control and experimental groups were analyzed by one way analysis of variance .Paired t- test was used to compare the pretest and post test of control and experimental groups..A probability of 0.05 or less was taken as statistically significant. The analysis and plotting of graphs were carried out using sigma plot 12.(Systat Software Inc.,USA)

The sit and reach parameter in pre test and post test in control and experimental groups were analyzed by one way analysis of variance .Paired t- test was used to compare the pretest and post test of control and experimental groups..A probability of 0.05 or less was taken as statistically significant. The analysis and plotting of graphs were carried out using sigma plot 12.(Systat Software Inc.,USA)

The experimental posttest 3, sit and reach score was not statistically significant from the control posttest 3 score.(t=1.774;p=0.081) for males ,but the experimental posttest 3, sit and reach score was also statistically significant from the control posttest 3 score.(t=3.230;p=0.002) for females. This gender difference will not influence the study results as maximal aerobic capacity and lung function will not change by either training and non training.

DISCUSSION:

In the present study, exercises and massage therapy was given for the cancer patients receiving chemotherapeutic drugs in experimental group for three days (60 mintes/day) in a week , massage therapy was given for hand and foot for 30 minutes in the evening. When comparing the pretest and posttest ,the overall total score of NCI-CTCAEV Neuropathy grading scale of the experimental group were highly signification from the control group. The improvement in the experimental group was better than the control group. The experimental posttest total score showed a significant difference from the control posttest 3 score.(c2=4270;p=<0.002), there was a drastic improvement in NCI CTCAE score from 1^st month to 3^rd month, which showed that exercises, massage therapy and health education on Home safety measures are effective in improving the nerve function among CIPN patients thereby ameliorating the neuropathy signs and symptoms

Exercise has been shown to improve the cardiovascular system, respiratory system, metabolic system, neuromuscular system, and endocrine system (Schneider et al, 2003). When cancer patients exercise, they may also experience a reduction in chemotherapy-related side effects. This study is similar to the present study findings.

In the present study, exercises and massage therapy was given for the cancer patients receiving chemotherapeutic drugs in experimental group for three days (60 mintes/day) in a week , massage therapy was given for hand and foot for 30 minutes in the evening. The overall total score of all functional scales, symptom scale and global health status of the experimental group were highly significant from the control group. The improvement in the experimental group was better than the control group. The experimental posttest 3 GHS score showed a gross difference from the control posttest 3 score. (c2=2858; p=<0.001), which showed that exercises, massage therapy and health education on Home safety measures are effective in improving the quality of

Rehabilitation exercises including physical and occupational therapy may be of help along with mild exercises or walking to overcome fatigue. Mild to moderate exercise to help promote energy are a boost for QOL even though they may feel tired.( Adamsen et al ,2009).This finding is similar to the present study report.

In the present study, exercises and massage therapy was given for the cancer patients receiving chemotherapeutic drugs in experimental group for three days (60 mintes/day) in a week, massage therapy was given for hand and foot for 30 minutes in the evening. The neuropathic pain score of the experimental group were highly significant from the control group. The improvement in the experimental group was better than the control group. The control posttest 2 ,Neuropathic pain score was significantly different from the experimental posttest 2 CON score.(c2=4247;p=0.001), The experimental posttest 3 neuropathic pain score showed no significant difference from the control posttest 3 score.(c2=3956;p=<0.087) which showed that there was a significant reduction in Neuropathic pain within the Experimental group, but not between the groups.

Mechanistically, there is emerging evidence to suggest that exercise and peripheral muscle stimulation may decreases axonal degeneration and maintain peripheral neuronal function (presumably via better blood flow in the region) (Park et al, 2015). Therefore, strategies for increasing overall physical activity and limb/region specific rehabilitation in cancer patients reporting CIPN should be incorporated in order to increase strength, improve balance, and quality of life presumably by decreasing the severity of pain symptoms in all types of PNP. Neuropathic pain following SCI is often only partially responsive to most interventions. Results from this study indicated that both acupuncture and massage therapy relieve SCI neuropathic pain.( Cecilia et al, 2010).This study is similar to the present study findings.

In the present study, the health teaching was given on home safety measures by ppt presentation among patients receiving chemotherapy drugs.The knowledge score of the experimental group were highly significant from the control group. The improvement in the experimental group was better than the control group. The experimental posttest 3 knowledge score showed a statistically significant difference from the control posttest 3 score. .(c2=3075;p=<0.004).which showed that there was a significant improvement in the knowledge regarding home safety measures among patients receiving cancer chemotherapy.

The successful treatment of patients with CIPN includes managing pain, preventing progression of this side effect and assuring patient safety while treating the cancer with optimal chemotherapy doses .It is the responsibility of the oncology nurse to develop a plan of care to manage the symptoms of CIPN, keep the patient safe and allow them to continue cancer treatment The use of both pharmacological and alternative treatments, can greatly improve the chances of successful chemotherapy treatment and CIPN management (Richardson, 2003).This finding is similar to the present finding report.

A detailed analysis was done in the present study in estimating the Vo2 max. The pretest Vo2 max score was statistically significant in males and females in both the groups, which indicated that the patients in both the groups fulfilled prefitness evaluation criteria and they can perform the aerobic exercises and physical exercises.

Considering the typical 15% improvement in peak VO₂ and 35% increase in estimated METs after CRET, these benefits translate into substantial reductions in subsequent mortality.( Franklin et al, 2013) . The above findings are similar to the present study, where in the present study also CRF was assessed by Vo2 max.

The findings in the present study indicate that combined training did not produce the expected strength and aerobic power benefits to cancer patients who had undergone radiotherapy and chemotherapy. However, aside from the non-significant change in VO2 max in particular, the increase in primarily upper limb muscle strength should lead help minimize the hemodynamic response to daily activities. This factor alone should be viewed as a positive outcome when it comes to increasing the patients’ longevity and quality of life by decreasing fatigue, muscle wasting, and energy loss in cancer survivors.

The detailed analysis was done in present study, the experimental posttest 3, sit and reach score was not statistically significant from the control posttest 3 score.(t=1.774;p=0.081) for males. but there was a statistically difference among the group’s pretest score. (t=3.103; p=0.003) among male patients. The experimental posttest 3, sit and reach score was also statistically significant from the control posttest 3 score. (t=3.230; p=0.002) for females, also noteworthy there was a statistically difference among the group’s pretest score.( t=3.669 ;p=0.001) among female patients.

The present study findings were similar to the study conducted by (Schmitz et al, 2014) that In the clinical setting ﬂexibility is often assessed using the sit and reach test. It is recommended that cancer patients participate in active stretching routines as part of a pre-exercise warm up. In the physical therapy setting, assisted stretching and modalities aimed at decreasing rigidity are standard of care.

In the present study of motor nerve conduction study showed that Latency and Amplitude of all nerves are affected. This finding was consistent with the results of ( Thompson et al, 1984) which studied prospectively with monthly neurologic examinations and conduction velocity determinations of median, peroneal, and sural nerves. The Sural nerve responses abruptly disappeared in six of peripheral nerves from four patients showed axonal degeneration and secondary myelin breakdown.

Fig 5a and 5b illustrates the scores of Vo2 max:The experimental posttest 3 vo2 max score was not statistically significant from the control posttest 3 score.(t=729;p=0.469) for males but the experimental posttest 3, vo2 max score was statistically significant from the control posttest 3 score.(t=3.198;p=0.002).for females This gender difference will not influence the study results as maximal aerobic capacity and lung function will not change by either training and non training. .

However, aside from the non-significant change in VO2 max in particular, the increase in primarily upper limb muscle strength should lead help minimize the hemodynamic response to daily activities. This factor alone should be viewed as a positive outcome when it comes to increasing the patients’ longevity and quality of life by decreasing fatigue, muscle wasting, and energy loss in cancer survivors.

Fig 6a and 6b illustrates the scores of sit and reach :The experimental posttest 3, sit and reach score was not statistically significant from the control posttest 3 score.(t=1.774;p=0.081) for males ,but the experimental posttest 3, sit and reach score was also statistically significant from the control posttest 3 score.(t=3.230;p=0.002) for females. This gender difference will not influence the study results as maximal aerobic capacity and lung function will not change by either training and non training.

However, aside from the non-significant change in VO2 max and flexibility , the increase in primarily upper limb muscle strength minimized the hemodynamic response to daily activities. This factor alone should be viewed as a positive outcome when it comes to increasing the patients’ longevity and quality of life by decreasing fatigue, muscle wasting, and energy loss in cancer survivors. Finally It is recommended that cancer patients should participate in active stretching routines as part of a pre-exercise warm up. In the physical therapy setting, assisted stretching and modalities aimed at decreasing rigidity are standards of care. Sufficient mobility must be obtained before heavy lifting , rather than simply prescribing a linear aerobic warmup (like tread mill walking or cycle ergometry) .Prior to resistance training, dynamic movements emphasizing muscle activation are preferred. This type of active stretching is preferably to traditional static stretching.(Schmitz et al 2014)

CONCLUSION:

This study has demonstrated that aerobic exercises, stretching exercises, strengthening exercises, balance training exercises , massage therapy, are effective in reducing the level of neuropathy, improving the Quality of life, reducing the neuropathic pain and improving the quality of life. The planned teaching program by powerpoint presentation are also effective in improving the knowledge on home safety measures among patients receiving cancer chemotherapy. The successful treatment of patients with CIPN includes managing pain, preventing progression of this side effect and assuring patient safety while treating the cancer with optimal chemotherapy doses .It is the responsibility of the oncology nurse to develop a plan of care to manage the symptoms of CIPN, keep the patient safe and allow them to continue cancer treatment. The use of both pharmacological and alternative treatments, can greatly improve the chances of successful chemotherapy treatment and CIPN management. Nurse educator and administrator can device standard protocol for CIPN assessment of cancer patients receiving neurotoxic chemotherapy and design early intervention to reduce the level of neuropathy, improve the quality of life, reduce the neuropathic pain and to gain on home safety measures.

REFERENCES:

1. Charles Loprinzi , R Pachman,D L Barton , J C Watson. (2011).Chemotherapy-Induced Peripheral Neuropathy: Prevention and Treatment, Clinical Pharmacology and Therapeutics 90(3):377-87

2. Cavaletti G, Frigeni B, Lanzani F. (2010). Chemotherapy-induced peripheral neurotoxicity assessment: a critical revision of the currently available tools: 46(494).

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4. Rao RD, Michalak JC, Sloan JA, et al.(2007). Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: Cancer. 110(9):2110-2118.

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3. 7.Hammack JE, Michalak JC, Loprinzi CL, et al. (2002).Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy :Pain. 98(1-2):195-203.

4. 8.Schneider, hershman, Loprinzi. (2015), Symptoms of CIPN: Advanced Exp Medical Biology,(862) 77-87.

5. 9. Adamsen, J. Midtgarrd, C. Andersen, et al. (2004).issue Transforming the nature of fatigue through execise,qualitative findings from a multidimensional exercise programme in cancer patients undergoing chemotherapy: European Journal of Cancer Care, (13)362-370 .

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Received on 14.06.2018 Modified on 17.06.2018

Res. J. Pharmacology & Pharmacodynamics.2018; 10(4): 179-199.

DOI: 10.5958/2321-5836.2018.00033.2

S No	parameter	Group	Median	Statistical analysis are given in fig
1	Knowledge on home safety measures of patient with CIPN	Control pre	50.500 (29.250 - 73.000 )	Given in fig 4
		post test 1	53.000 ( 30.000 - 72.750)
		post test 2	55.000 (33.500 -74.000)
		post test 3	53.500 ( 40.000 - 76.000 )
		Experimental pre	45.500 ( 28.500 - 62.000 )
		post test 1	58.500 ( 27.750 - 72.000 )
		post test 2	63.000 ( 48.250 - 78.000 )
		post test 3	73.000 ( 55.500 - 81.750 )


Figure 1 a: Effectiveness of care bundle approach on CIPN-sensory, of control and experimental groups. The middle red line is median and the blue line is the mean (n = 60 each). The c2 and P values are by Friedman RM ANOVA of the respective groups. The control and experimental groups are compared by Mann-Whitney rank sum test. For the Pre-test the ‘T’ and ‘P’ values are 3711 and 0.663 respectively; For the Post-test 1 the ‘T’ and ‘P’ values are 3604 and 0.889 respectively; For the Post-test 2 the ‘T’ and ‘P’ values are 3828 and 0.278 respectively; For the Post-test 3 the ‘T’ and ‘P’ values are 4292 and < 0.001 respectively. a – Significantly different from the respective Pre-test. b – Significantly different from the respective control group.

Figure 1 b: Effectiveness of care bundle approach on CIPN-motor, of control and experimental groups. The middle red line is median and the blue line is the mean (n = 60 each). The c2 and P values are by Friedman RM ANOVA of the respective groups. The control and experimental groups are compared by Mann-Whitney rank sum test. For the Pre-test the ‘T’ and ‘P’ values are 3854 and 0.215 respectively; For the Post-test 1 the ‘T’ and ‘P’ values are 4063 and 0.017 respectively; For the Post-test 2 the ‘T’ and ‘P’ values are 39.43 and 0.080 respectively; For the Post-test 3 the ‘T’ and ‘P’ values are 31.79 and 0.044 respectively. a – Significantly different from the respective Pre-test. b – Significantly different from the respective control group.


Figure 2 g :Effectiveness of care bundle approach Quality of life – fatigue (fa) of control and experimental groups. The middle pink line is median and the blue line is the mean (n = 60 each). The c2 and P values are by Friedman RM ANOVA of the respective groups. The control and experimental groups are compared by Mann-Whitney rank sum test. For the Pre-test the ‘T’ and ‘P’ values are 4887 and <0.001 respectively; For the Post-test 1 the ‘T’ and ‘P’ values are 4425 and <0.001 respectively; For the Post-test 2 the ‘T’ and ‘P’ values are 4046 and 0.027 respectively; For the Post-test 3 the ‘T’ and ‘P’ values are 3603 and 0.885 respectively. a – Significantly different from the respective Pre-test. b – Significantly different from the respective control group.

Figure 2 h: Effectiveness of care bundle approach on Quality of life – Vomiting of control and experimental groups. The middle pink line is median and the blue line is the mean (n = 60 each). The c2 and P values are by Friedman RM ANOVA of the respective groups. The control and experimental groups are compared by Mann-Whitney rank sum test. For the Pre-test the ‘T’ and ‘P’ values are 3580 and 0.787 respectively; For the Post-test 1 the ‘T’ and ‘P’ values are 3499 and 0.466 respectively; For the Post-test 2 the ‘T’ and ‘P’ values are 3271 and 0.054 respectively; For the Post-test 3 the ‘T’ and ‘P’ values are 2953 and < 0.001 respectively. a – Significantly different from the respective Pre-test. b – Significantly different from the respective control group.

S.No	para meter	Group	Median (Percentile) (25-75)	Statistical analysis
		post test 1	16.500 (8.000 - 20.000)
		post test 2	12.000 (8.000 - 20.000)
		post test 3	11.000 (4.000 - 23.000)
		Experimental pre	16.000 (11.000 - 20.000)
		post test 1	12.000 ( 6.250 - 18.000 )
		post test 2	8.500 (5.000 - 13.750 )
		post test 3	7.000 ( 4.000 - 13.000 )