INTRODUCTION:

Head and neck cancers usually begin in the squamous cells that line the moist, mucosal surfaces in the head and neck (for example, inside the mouth, the nose, and the throat). These squamous cell cancers are often referred to as squamous cell carcinomas of the head and neck).

Fig:1

Cancers of the head and neck are further categorized by the area of the head or neck in which they begin. These areas are described above and labeled in the image of head and neck cancer regions.

AIM AND OBJECTIVES:

Aim:

To evaluate quality of life in patients on concurrent chemo radiotherapy with cisplatin in head and neck cancer.

Objective:

To measure the quality of life and pharmaceutical care and toxicity profile of cisplatin with radiotherapy in head and neck cancer.

Plan of work:

The work is planned to carry out as follows:

· To include head and neck cancer patients.

· To design a patient data collection form and standard questionnaire H& N 35.

· To collect all the data required for the study from radiotherapy out -patient and in patient department.

· To analyze the data and provide the feedback of results to the physician (prescriber) and submit the safety data of cisplatin and adverse reactions of the drug.

· To counsel the patients regarding the usage and effects of medications.

METHODOLOGY:

Study site:

A Non experimental prospective observational study was conducted on head and neck cancer patients in radiotherapy department, GOVERNMENT GENERAL HOSPITAL, Guntur, Andhra Pradesh.

Study duration:

The study was carried out between December 2016 and May 2017.

Inclusion criteria:

· A patient who suffered from various types of head and neck cancer.

· Consented males and females above age 18 years.

· A patient who is concurrent chemoradiotherapy with cisplatin for any cancer of head and neck cancer.

Exclusion criteria:

· Patients who suffered from cancers, other than head and neck cancers.

· Patients with head and neck cancer under 18 years are excluded.

· Patients who have recurrent and remission of head and neck cancers.

· Female patients with pregnancy are excluded.

· Patients with severe heart disease and lung disease are excluded.

Study design:

A Non Experimental prospective observational study.

STUDY METHOD:

· The study is conducted in the Government General Hospital, Guntur, a1300 bedded tertiary care hospital.

· All patients with head and neck cancer patients will be included in the study.

· Most of the patients visiting the hospital are from rural areas

· Patients were screened for RFT/LFT/RBS/CBP were considered.

· Evaluation of clinical symptoms, RFT/LFT/RBS/CBP levels in patients on cisplatin, safety parameters was assessed.

· The baseline knowledge of the patients on the disease, complications, regular blood glucose monitoring, diet, lifestyle modifications and medication adherence is assessed using a questionnaire.

· Patients are then counseled about disease, diet, lifestyle modifications and medication adherence.

· Patients are reviewed periodically (i.e., Every 3 months) for the improvement in their prognosis of cancer and improvement in general condition.

OBSERVATIONS AND RESULTS:

SOCIODEMOGRAPHIC EPIDEMIOLOGICAL DATA:

Age wise distribution of cancers:

Table: 1 Age wise distribution of cancers

AGE	No. of Patients	Percentage (%)
0-10	10	2.77
11 to 20	14	3.87
21 to 30	20	5.54
31 to 40	113	31.30
41 to 50	57	15.78
51 to 60	80	22.16
61 to 70	45	12.46
71 to 80	11	3.04
81 to 90	11	3.04

Fig: 2 The table describes the Age wise distribution of patients with Cancer; According to the data the patients with Age group between 31 to 40 were highly affected and age group between 0 to 10 were less affected.

Gender wise distribution of patients with cancer:

Table 2 describes the gender wise distribution of patients affected with cancer a total of 361 patients was diagnosed with different types of cancers; Out of which 235 (65%) were females and 126 (34%) were males.

Gender	Number	Percentage
Female	235	65%
Male	126	34%

Fig:3 Gender wise distribution of patients affected with cancer

Area wise Distribution of Patients with Cancer

Table 3 describes the Area wise distribution of patients with cancer; Out of 361 patients 143 (40%) belongs to the Urban area whereas 218 (60%) belongs to Rural area

Area Wise Distribution of Patients with Cancer
Area	Number	Percentage (%)
Rural	218	60%
Urban	143	40%

Fig:4. Area wise distribution of patients with cancer

Type wise distribution of cancers

Table 4; Type wise distribution of cancers categorize different types of cancer in which cervix cancer patient are more 80(22%) and post cricoids patients are 11(3.04%)

S. No	Type of cancer	Number of patients	Percentage (%)
1	Myeloid leukemia	11	3.04
2	Breast cancer	48	13.29
3	Osteaosarcoma	1	0.277
4	Chondriosarcoma	1	0.277
5	Hepatocellular carcinoma	7	1.93
6	Vault	9	2.49
7	Choriocarcinoma	3	0.83
8	Pancreas	4	1.10
9	Gallbladder	3	0.83
10	Vulva	4	1.10
11	Stomach	9	2.49
12	Esophagus	1	0.277
13	Bladder	7	1.93
14	Periampullary	4	1.10
15	Prostate	2	0.55
16	Pennis	6	1.66
17	Lymphomas	9	2.49
18	Ovary	19	5.26
19	GBM	4	1.10
20	Colon	21	5.81
21	Lung	21	5.81
22	Multiple myeloma	3	0.83
23	Cervix	80	22.16
24	Thyroid	11	3.04
25	Tongue	12	3.32
26	Parotid	2	0.55
27	Supraglottis	12	3.32
28	Nasopharynx	3	0.83
29	Lower lip	1	0.277
30	Oral cavity	3	0.83
31	Oropharynx	1	0.277
32	Post cricoids	11	3.04
33	Vocal cord	2	0.55
34	Tonsils	1	0.277
35	Angle of mouth	1	0.277
36	Hypopharynx	3	0.83
37	MUO neck	3	0.83
38	Secondary neck	2	0.55
39	Hard palate	3	0.83
40	Soft palate	1	0.277
41	Recurrent buccal mucosa	2	0.55
42	Buccal mucosa	4	1.10
43	Alveoli	1	0.277
44	Larynx	1	0.277
45	Cheek	1	0.277
46	RMT	2	0.55
47	Glottis	1	0.277

Fig: 5: Type wise distribution of cancer

AGE WISE DISTRIBUTION OF PATIENTS WITH HEAD AND NECK CANCER:

Table5: Age wise Distribution of Patients with Head and Neck Cancer

S. No	Age Group	Number of Patients	Percentage (%)
1.	<30	2	2.702
2.	31-40	10	13.513
3.	41-50	14	18.918
4.	51-60	19	25.675
5.	61-70	19	25.675
6.	>70	10	13.513

Table 5: Describes age wise distribution of Patients with Head and Neck Cancer that shows that between age group 51-70(25.675%) are more suffered with head and neck cancer.

Fig: 6: age wise distribution of Patients with Head and Neck Cancer

DISTRIBUTION OF PATIENTS BY STAGE OF HEAD AND NECK CANCER:

Table 6-: Distribution of Patients with Stage of Cancer

S.No	Stage	No of Patients	Percentage (%)
1.	I	1	1.351
2.	II	20	27.027
3.	III	29	39.189
4.	IV A	11	14.864
5.	IV B	13	17.567
6.	IV C	0	0

Table 6: In distribution of patient with stage of cancer describes that patient are more diagnosed with stage II(27.027%) and stage III (39.189%)cancer

Fig: 7-: Distribution of Patients with Stage of Cancer

DISTRIBUTION OF PATIENTS BASED ON EDUCATIONAL STATUS:

Table 7: Distribution of patients based on Educational status

S. No.	Educational status	No. of patients	Percentage (%)
1.	Illiterates	60	81.108
2.	Primary education	10	13.513
3.	Secondary education	3	4.054
4.	Graduates	1	1.351

Table7: describes the who are suffering from head and neck cancer are illeterates(81.1)and primary education(13.531%)

Fig: 8: : Distribution of patients based on Educational status

DISTRIBUTION OF PATIENTS BASED ON FOOD HABITS:

Table 8: Distribution of Patients Based on Food Habits

S. No	Food habits	No. of. Patients	Percentage (%)
1.	Vegetarian	2	2.702
2.	Mixed diet	72	97.29

Table8: table describes most of patients are having habit of taking mixed diet(2.702%) rather than vegetarian(97.29%)

Fig: 9: Distribution of Patients Based on Food Habits

DISTRIBUTION OF PATIENTS BASED ON LOCATION:

Table9: Categorization of patients based on Locality

S. No	Location	No. of Patients	Percentage (%)
1.	Urban	14	18.918
2.	Rural	60	81.081

The table describes that 14 (18.918%) of patients belongs to Urban area and about 60 (81.08%) of patients are from Rural area.

Fig: 10: Distribution of patients based on location

TYPE WISE DISTRIBUTION OF HEAD AND NECK CANCER IN FEMALES:

Table10: Distribution of patients based on different cancer

S. No	Diagnosis	Number of Patients	Percentage (%)
1.	Tongue	5	27.77
2.	Parotid	1	5.55
3.	Lower lip	1	5.55
4.	Oral cavity	1	5.55
5.	Alveoli	1	5.55
6.	Post cricoid	9		50

This table describes about different types of cancers in female patients suffering mostly with postcricoid (50%) out of 18 females.

Fig: 11 Distribution of patients based on different cancer in females

TYPE WISE DISTRIBUTION OF HEAD AND NECK CANCER IN MALES:

Table 11: Distribution of patients based on different cancer

S. No	Diagnosis	Number of Patients	Percentage (%)
1.	Tongue	7	12.28
2.	Parotid	1	1.75
3.	Supraglottis	12	21.05
4.	Nasopharynx	3	5.26
5.	Oral cavity	2	3.50
6.	Oropharynx	1	1.75
7.	Post cricoids	4	7.01
8.	RMT	2	3.50
9.	Glottis	1	1.75
10.	Vocal cord	2	3.50
11.	Tonsils	1	1.75
12.	Angle of mouth	1	1.75
13.	Hypopharynx	3	5.26
14.	MUO neck	3	5.26
15.	Hard palate	3	5.26
16.	Soft palate	2	3.50
17.	Buccal mucosa	7	12.28
18.	Larynx	1	1.75
19.	Cheek	1	1.75

This table describes about different types of cancers in male patients suffering mostly with supraglottis (21.05%) out of 57 males.

Fig: 12: Distribution of patients based on different cancer

DISTRIBUTION OF HEAD AND NECK CANCER PATIENTS BASED ON HBs Ag STATUS and NONE

Table 12: categorization of patients based on viral status

Viral status	No of Patients	Percentage
HBs Ag	1	1.35
None	73	98.6

The above table describes that 1 (1.35%) of patients are HBs Ag positive.

Fig: 13: Distribution of head and neck cancer patients based on Hbs Ag status and none

CATEGORIZATION BASED ON FAMILY HISTORY IN HEAD AND NECK CANCER PATIENTS:

Table 13: Distribution of patients based on Family history

S. No	Family history	No. of Patients	Percentage (%)
1.	Yes	0	0
2.	No	63	85.13
3.	Not known	11	14.86

From the above table, we can know that no patient had a family history of head and neck cancer. About 11 (14.12%) of patients don’t know about their family history of cancer.

Fig: 14: Distribution of patients based on Family history

CATEGORIZATION OF OC CUPATIONAL STATUS IN HEAD AND NECK CANCER PATIENTS

Table-14: Categorization of patients based on occupational stat

S. No	Occupational status	No. of Patients	Percentage (%)
1.	Employee	2(%)	2.702
2.	Self employed	20(%)	27.02
3.	Daily wage	34(%)	45.94
4.	Not working	18(%)	24.32

The above table describes that 34 (45.94%) of patients are daily wagers and only about 2 (2.702%) patients are employees.

Fig 15: Categorization of patients based on occupational status

CATEGORIZATION OF STUDY PARTICIPANTS BASED ON SOCIAL HABITS IN HEAD AND NECK CANCER PATIENTS:

Table 15: Categorization of study participants based on social habits

S. No	Social history	Number of patients	Percentage (%)
1.	Smoking	42	56.756
2.	Alcohol	12	16.216
3.	Betel nut	10	13.513
4.	Occupational Exposure	10	13.513

From the Table15-; About 42 (56.75%) patients have the habit of smoking and about 12 (16.216%) patient have habit of alcohol and 10 (13.513%) patients don’t have any history of social habits.

Figure-16: Categorization of study participants based on social habits

CATEGORIZATION BASED ON HISTOPATHOLOGICAL CLASS OF HEAD AND NECK CANCER

Table 16: Categorization Based on Histopathological Class of Head and Neck Cancer

S. No	Histopathological class	No. of patients	Percentage (%)
1.	Squamous cell carcinoma	74	100

Table 16 describes the categorization of Patients Based on their Histopathological Class of Head and Neck Cancer; Out of 74 patients 74 (100%) were diagnosed as Squamous cell carcinoma.

Fig: 17-: Categorization Based On Histopathological Class of Head and Neck Cancer

CATEGORIZATION OF PATIENTS BASED ON MODE OF TREATMENT

Table-17: Categorization of Patients Based on Mode of Treatment.

S. No	Mode of treatment	No. of patients
1.	Concurrent	20
2.	Radiation	54

The above table decribes that patients on concurrent are 20 and radiation are 54

Fig: 18: Categorization of Patients Based on Mode of Treatment

CATEGORIZATION OF PATIENTS BASED ON RECURRENCE OF CANCER

Table 18: Categorization of patients based on recurrence of cancer.

S. No	Recurrence	No. of patients
1.	Yes	4
2.	No	71

The table describes about No of recurrence patients are 4 and with out recurrence are 71 in six months of duration

Fig: 19: Categorization of patients based on recurrence of cancer.

ASSESSMENT OF QUALITY OF LIFE:

· Quality of life was assessed by using the FACT- H&N QLQ Questionnaire.

· The FACT- H&N QLQ incorporates five functional scales (additional, physical, functional, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting).

· And a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, dysphasia, constipation and diarrhea) and perceived financial impact of the disease

FUNCTIONAL SCALE DOMAINS IN EORTC QLQ C-30

Table-19: Functional Scale

S. NO.	DOMAINS	MEAN ± STANDARD DEVIATION
S. NO.	DOMAINS	Before Treatment	After Treatment	P-Value
1.	Additional concerns	13.16±11.8	20.16±16.7	<0.0001
2.	Emotional well-being	20.63±15.18	35.75±18.23	<0.0001
3.	Functional well-being	13.66±11.60	28.63±16.53	<0.0001
4.	Physical well-being	7.16±4.70	25.80±15.03	<0.0001
5.	Social Functioning	10.50±1.76	32.90±10.90	<0.0001

ADDITIONAL CONCERNS:

Before Treatment: - 13.16±11.8

After Treatment: - 20.16±16.7 P-Value: <0.0001

Fig: 20

SOCIAL FUNCTIONING:

Before Treatment: - 10.50±1.76

After Treatment: - 32.90±10.90

P-Value: - <0.0001

Fig: 21

PHYSICAL WELL-BEING
Before Treatment: - 7.16±4.70
After Treatment: - 25.80±15.03 P-Value: <0.0001

Fig: 22

EMOTIONAL WELL-BEING:

Before Treatment: - 20.63±15.18
After Treatment: - 35.75±18.23
P-Value: <0.0001

Fig:23

FUNCTIONAL WELL-BEING:
Before Treatment: - 13.66±11.60
After Treatment: - 28.63±16.53
P-Value: <0.0001

Fig: 24

TOXICITY PROFILE OF PATIENTS ON CONCURRENT CHEMORADIOTHERAPY AND RADIOTHERAPY:

Table-20: Patients Suffering with Adr’s In Both Chemotherapy and Radiotherapy

Type of treatment	Total No of patients	No of patients with ADR’S
Concurrent Chemotherapy	20	20
Radiotherapy	54	54

This is about patients suffering from adrs in both concurrent chemotherapy and radiotherapy are 20 and 54

Fig: 25: Patients suffering with adr’s in both chemotherapy and radiotherapy

CONCURRENT CHEMORADIOTHERAPY INDUCED ADVERSE DRUG REACTIONS:

Table-21: - categorization based on chemotherapy induced ADR’S

Type of reaction	No of patients	Percentage
Nausea	8	40
Vomiting	8	40
Oral ulcers	15	75
Neutropenia	10	50
Anemia	18	90
Thrombocytopenia	18	90
Weight loss	17	85

This describes about patients on concurrent chemoradiotherapy are more suffering from weight loss(85%), anemia(90%), thrombocytopenia (90%)

Fig: 26: categorization based on chemotherapy induced ADR’S

RADIATION INDUCED ADVERSE DRUG REACTION:

Table-22: - categorization based radiation induced ADR’S

Type of reaction	No of patients	Percentage
Dermatitis	50	92
Trismus	30	55
Mucositis	52	96
Dysphagia	45	83
Odynophagia	25	46
Xerostomia	53	98
Nausea and Vomitings	10	18

The above table describes about patients on radiotherapy are suffered from dermatitis(92%), mucositis(96%), xerostomia(98%)

Fig: 27: categorization based radiation induced ADR’S

DISCUSSION:

During a 6 months study, 74 patients who were diagnosed with head and neck cancer and who met the inclusion criteria were taken as study subjects. The prevalence of ADRs varies from subject to subject because of the inter subject variability towards the drugs administered

Subjects were recruited based on criteria that were set in the protocol. Subjects for concurrent chemo radiotherapy were selected based on performance status of the patient that assess the capability of the patient to withstand the chemotherapy drugs and their ADR’s. ECOG (Eastern Cooperative Oncology Group) performance status scale, which provides with the grading and relative description is used in this study.

As similar to the study, which is conducted by Susan Urba, et al., (2012) - Advanced head and neck cancer patients to assess the overall survival rate using the quality assessment scale score as prognostic factors by giving treatment as cisplatin monotherapy. The study population of 795 out of which 704 subjects are suitable for the study. It was conducted during the year 2012. They have used FACT – H & N questionnaire to assess the quality of life. Age above 65 yrs, site of disease, ECOG are considered as prognostic factor for survival as were baseline scores on four FACT-H&N subscales (physical well-being, emotional well-being, functional well-being, additional concerns-H&N; HRs = 0.82–0.94; all P< 0.002) and prior surgery/radiotherapy (HR = 0.76); and baseline scores of the FACT-H&N subscales of physical well-being, social/family well-being, and additional concerns-H&N (HRs = 0.89–0.94; all P ⩽ 0.014 per table).

In our study to assess quality of life of the patient, we used FACT-H&N questionnaire (version-9), ECOG performance status. The patients who met the inclusion criteria set by us are started giving treatment with cisplatin and five days radiation in a week of age above 18 years and assessed quality of life in both radiation and concurrent chemo radiation patients by filling the questionnaire FACT - H & N which consist of several parameters related to quality of life viz., emotional well being, physical score, social well being, functional well being and additional concerns.

We obtained an overall significance of P<0.0001 both prior to treatment and after the treatment.

As compared to the above study, their P value is found to be <0.002 and in the present study the P value is <0.0001that shows that the present study conducted by us is highly significant. The patients who are involved in our study have achieved better quality of life when compared to the above said study.

During the history collection it was found that smoking consumption and alcohol consumption were the main reasons for head and neck cancers than other related etiologies as said in a study by Cristina Hernández-Vila, et al., (2017).

As similar to the study, which is conducted by Maghous.A, et., (2017) – This is a prospective study to evaluate cisplatin induced toxicity, as once-weekly regimen in HNC during concurrent chemoradiotherapy (CCRT) to optimize its administration. From 01 January 2015 to 11 May 2015 study was conducted, and of all eligible patients treated with chemoradiation regimens containing a low dose of cisplatin were collected by the Department of radiotherapy in National Institute of Oncology in Morocco. Cisplatin was used weekly at 40 mg/m2 with adequate hydration and premedication in all patients. A complete blood count and renal function tests were done prior to each cycle of chemotherapy to evaluate toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). A total of 96 patients were eligible for the analysis. Mean age, PS, initial weight, enteral nutrition, cisplatin mean dose, use of oral Ondansetron and baseline serum tests did not differ significantly. However, weight loss was significantly noted among HNC group compared with 6.06 ± 2.92 kg respectively. Toxicity was observed only in 16 (20%) patients after the 4th week of treatment especially among HNC group. The neutropenia and thrombocytopenia were significantly greater for patients of HNC. In multivariate analysis, only a subtype of HNC (OR, 1233; 95% CI, 16-95 103; P=0.001) and grade 2 emetogenicity (OR, 34.8; 95% CI, 2.1-583; P=0.014) were significantly associated with an increased risk for cisplatin toxicity. Whereas, less than 4 weekly cisplatin treatment (OR, 0.4; 95% CI, 0.1-0.9; P=0.046) was associated with a significantly reduced risk. The data have revealed that individuals with HNC were at a significantly higher risk for cisplatin induced toxicity during CCRT and suggest that the once-weekly smaller dose of cisplatin regimen and conventional prophylactic procedures of administration might be effective for protection against the renal toxicity of cisplatin.

In the present study the patients who are under concurrent chemoradiotherapy of all eligible patients treated with chemoradiation regimens; cisplatin was used weekly at 50 mg with adequate hydration and premedication in all patients for six cycles. A complete blood count and renal function tests were done prior to each cycle of chemotherapy to evaluate toxicity under the guidance of a physician. A total of 20 patients were eligible for the analysis. However, weight loss was significantly noted among 17 out of 20 HNC group compared with percentage of 85%. Toxicity was observed patients after the 3^rd week of treatment among HNC group. The neutropenia and only in 10 (50%) thrombocytopenia only in 18 (90%) were significantly greater for patients of HNC and grade 1 emetogenicity only in 8 (40) were significantly associated with an increased risk for cisplatin toxicity. Patient whose performance status is very poor, then preferred the regimen cisplatin only for four weeks. Whereas, less than 4 weekly cisplatin treatment was associated with a significantly reduced risk. The data have revealed that individuals with HNC were at a significantly higher risk for cisplatin induced toxicity during CCRT and conventional prophylactic procedures of administration might be effective for protection against the renal toxicity of cisplatin.

Out of 96 subjects 16 subjects were observed toxicity with cisplatin at the dose of 40 mg/m²after the 4th week of therapy in the above said study and in the present study; we observed the toxicity with cisplatin at the dose of 50 mg after 3^rd week of therapy. We have taken preventive measures to prevent the oral infections like candidiasis by prescribing medication flucanazole and to maintain dental hygiene mouth washers are made to be used by patients. Due to high incidence of neutropenia and thrombocytopenia antibiotics like ciprofloxacin and metronidazole are administered who is suffering with fever and systemic infections.

Apart from above mentioned study, we have noticed oral ulcers in 15 (75%) and anemia in 18 (90%) of total 20 members.Even we considered the adverse reactions occurred during radiation alone. Besides concurrent chemo radiotherapy there are 54 patients under the radiation. Subjects after receiving a second week of radiation had encountered with different types of toxic reactions such as Dermatitis in 50 (92%), Trismus in 18 (33%), Mucositis in 52 (96%), Dysphasia in 35 (64%), Odynophagia in 25 (46%), Xerostomia in 53 (98%) and Nausea and Vomiting in 10 (18%) of total 54 patients.

Hence a supportive therapy for symptomatic relief was suggested to the patients whereby the physician accepted the suggestions of the clinical pharmacist prescribed the supportive medications for ADR’swhich helped the patient to cope up with them. This had a major hand in improving the QoL of the patient and progression on the performance status. Apart from this, we, clinical pharmacists counseled the patients regarding disease, medication and diet that could take viz., Buttermilk, porridge, malts, non-irritant juices like cane sugar, banana, etc, they helped the patient to gain physical strength and cooperate with the treatment. This made patient to recover faster.

CONCLUSION:

Our study concluded that the incidence of ADRs associated with drug toxicities in concurrent chemotherapy patients and patients with radiotherapy alone. Regular follow up and provision of pharmaceutical care is a key factor to manage the ADRs and complications. By creating awareness and providing pharmaceutical care on disease and usage of drugs, medication adherence and quality of life of the patient was improved.

The need for provision of pharmaceutical care is necessary to improve quality of life of both concurrent chemotherapy patients and patients with radiotherapy alone to manage all the possible ADRs and complications associated with the drugs and disease progression. Prescription errors, administration errors, possible ADRs were avoided due to strict follow-up by the pharmacist. Along with physicians, nurses and clinical pharmacists have a great role in the management of ADRs and improvement of patient’s quality of life.

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Received on 08.12.2017 Accepted on 18.02.2018

Asian J. Pharm. Res. 2018; 8(1): 21-31.

DOI: 10.5958/2231-5691.2018.00005.9