this prospective study was conducted among 488 patients admitted to oncology ward of our hospital , over a period of 1 year , after obtaining the approval of the institutional ethics committee ( iec 176/2012 ) . it was an observational , focused pharmacovigilance study carried out as a part of the pharmacovigilance program of the hospital from january 1 , 2013 , to december 31 , 2013 . after obtaining informed consent , data on adrs were collected from the cancer patients belonging to both gender and of all ages , who were receiving either taxane  based or vinca - based cancer chemotherapy under any standard regimen . those patients who did not receive drugs belonging to either of these groups as part of drug regimen were excluded from the study . no change in the treatment decision , schedule , or duration of cancer chemotherapy was made as a part of the study . the patients who were admitted following the infusion were monitored for adverse effects till their discharge from hospital . the drug effects which were described by the patients and effects which were diagnosed and documented by the physician during the infusion visit and the follow - up period were recorded . patients demography , drug , dose , type of adr , severity , causality , and outcome of the treatment of adr were noted and reported in the indian pharmacopoeia commission ( ipc ) form . the who causality assessment scale is the one recommended by the who uppsala monitoring center and classifies adr as certain , probable , possible , unlikely , conditional , and unassessable . the naranjo 's algorithm is a questionnaire  based scale consisting of ten objective questions with three types of answers , yes , no , or do not know . scores are given accordingly , and the drug reaction can be classified as definite , probable , possible , and doubtful based on the total score . in naranjo 's algorithm , if there were alternate causes particularly other drugs in case of multi - drug regimen then the score for that question would be negative . preventability and severity of adrs were assessed by modified schumock and thornton scale and modified hartwig et al . the modified schumock and thornton scale classifies adrs as definitely preventable , probably preventable , and not preventable based on a set of questions for each level . the modified hartwig and siegel scale classify the severity of adr as mild , moderate , or severe with various levels according to factors such as requirements for change in treatment , duration of hospital stay , and disability produced by the adr . this was uploaded weekly on the vigiflow database for assessment by national coordinating centre , ipc which was reported to uppsala monitoring center  a who program for international drug monitoring . a total of 488 patients on microtubule - damaging anticancer drugs ( taxanes and vinca alkaloids ) were admitted to oncology ward during the above period . among them , 97 adrs were reported . majority of adrs occurred in the age group of 4160 years ( n = 45 , 46.4% ) with a female preponderance ( n = 67 , 69.1% ) . of the 180 male patients , 19 ( 10.56% ) reported with adrs and similarly of the 308 female patients , 39 ( 12.66% ) reported with adrs . the observations for sex distribution of adrs were analyzed statistically using chi - square test . the sex wise difference in the occurrence of adrs was statistically not significant ( p = 0.481 ) . of the adrs reported , 73 ( 75.3% ) were from those being treated for an early stage of the tumor , whereas 24 ( 24.7% ) were from patients being treated for an advanced malignancy . of the total reactions , 34 ( 35.1% ) were from those who received anticancer drugs as the primary modality of treatment , 42 ( 43.3% ) were from those who received the drugs as adjuvant therapy , 16 ( 16.5% ) from those who received as neoadjuvant therapy , and 5 ( 5.2% ) of the reactions were from those who received as palliative care . only 21 ( 21.6% ) reactions were from those who received these drugs as monotherapy , while 75 ( 77.3% ) reactions were from those who received these drugs as a part of a regimen . the median cycle number at which adrs were reported is 3 ( interquartile range [ iqr ] 15 ) . results revealed that gastrointestinal system 39 ( 40.2% ) was the most affected organ system followed by bone marrow 32 ( 33% ) , skin 8 ( 8.2% ) , kidney , central nervous system and others 6 ( 6.2% ) [ figure 1 ] . frequency of adverse drug reactions categorized based on organ involved the various indications for the use of taxanes were tumors of head and neck , lung , peritoneal , and gynecological tumors . the frequently reported adrs among taxanes were anemia 11 ( 18.6% ) , diarrhea 10 ( 16.9% ) , candidiasis 7 ( 11.9% ) followed by peripheral neuropathy 4 ( 6.8% ) [ figure 2 ] . * others = respiratory tract infection thrombocytopenia , vomiting , * * others = cellulitis , elevated liver enzymes , angular stomatitis , flushing of face , photodermatitis , symptomatic hyponatremia , tinea corporis , alopecia , fever , glossitis , numbness , skin discoloration the various indications for the use of vinca alkaloids were tumors of head and neck and childhood tumors . the frequently reported adrs among vinca alkaloids were febrile neutropenia 9 ( 23.7% ) , candidiasis 8 ( 21.1% ) , vomiting 6 ( 15.8% ) , followed by anemia 3 ( 7.9% ) , and obstipation 3 ( 7.9% ) [ figure 3 ] . adverse drug reaction types with vinca alkaloids . * others = peripheral neuropathy , abdominal pain , diarrhea , neutropenia , thrombocytopenia , urinary tract infection , weakness most of the reported adrs were type a reactions as per the adr classification by rawlin and thomson . predictability analysis showed that 43 ( 44.3% ) of the reactions were not predictable while 54 ( 55.7% ) were predictable . according to modified shumock and thornton scale ( n = 50 , 51.5% ) , followed by 27 ( 27.8% ) of the reactions  not preventable  while reactions like vomiting and neutropenia belonged to the category  definitely preventable . based on modified hartwig and siegal scale of severity assessment , most of the reactions were of  mild level 1  severity , except for candidiasis and febrile neutropenia , which were of  moderate level 3  severity . the who causality assessment scale indicated 28 ( 28.9% )  probable  and 69 ( 71.1% )  possible  but no  certain  reactions . naranjo 's algorithm indicated 48 ( 49.5% )  probable  with score ranging from 5 to 8 and 49 ( 50.5% )  possible  reactions with a score ranging from 1 to 4 [ table 1 ] . however , the grade of causality for each adr remained low due to the presence of co - administered drugs . of the reported cases , 69 ( 71.1% ) received either specific or symptomatic treatment while 28 ( 28.9% ) required no treatment . the median duration of hospital stay of those who required admission was 7.50 ( iqr 020 ) . from the study , it was found that 85 ( 87.5% ) recovered from the reaction , although none had fatal adrs . the remaining 12 ( 12.4% ) cases either continued to have the reaction during the study or else their reaction treatment outcome was unknown . an adr , as defined by the who , is  a response to a medicine which is noxious and unintended , and which occurs at doses normally used in man . according to lazarou et al . in 1998 , adrs are considered fourth to sixth leading cause of death in the united states with an incidence of 0.13% fatal adrs requiring hospital admissions . the plant alkaloids ( taxanes and vinca alkaloids ) , exert their antineoplastic effects by interfering with microtubule function , leading to inhibition of mitosis and apoptosis . vinca alkaloids cause destabilization of the mitotic spindle , whereas taxanes cause disorganized stabilization of microtubule ultimately resulting in cell cycle arrest . taxanes are the leading agents in the treatment of various malignancies including breast cancer , ovarian cancer , prostate cancer , kaposi 's sarcoma , squamous cell carcinoma of the head and neck , esophageal cancer , lung cancer , and bladder cancer . vinca alkaloids are used in various treatment protocols of hematological malignancies and solid tumors including germ cell cancer , lung cancer , neuroblastoma , ewing sarcoma , and multiple myeloma . taxanes and vinca alkaloids being natural plant products , though apparently considered as safer drugs , like all other drugs they too show some adrs in various patient conditions . the incidence rate of adverse reactions in this study was found to be comparatively low when compared to other studies . this lower incidence rate could be due to delivering periodic adr awareness classes to treating physicians and nurses , active involvement of clinical pharmacy and postgraduate students of pharmacology in clinical activities and coordination of quality control unit in the hospital . in this study , we found that majority of the patients were females ( 69.1% ) which is consistent with findings in other studies . in india , most common cancer among males is oropharyngeal cancer followed by bronchogenic carcinoma with oropharyngeal cancer having surgical resection and irradiation as the modality of treatment . thus , there was a proportionately higher ratio of females who were prescribed micro - tubule damaging drugs which account for the predominance of adverse reactions in them . analysis of the age - wise distribution showed the predominance of patients in the age group of 4160 years ( 46.4% ) which is again similar to reports of previous studies . the primary indications of the microtubule - damaging drugs were for breast , ovarian , cervical , endometrial carcinomas , and other solid tumors which were more prevalent among geriatric patients . the presence of comorbid illnesses and usage of multiple drugs in them also could attribute to the adverse reactions in them . this could also be because , in elderly patients , the metabolizing capacity and the excretory functions are reduced , leading to accumulation of drugs in the body and thus increasing the risk of adrs . in this study , the different treatment plans adopted depend on a variety of factors such as the staging of cancer , cost of the treatment plan , patient and physician - related factors . the causality attributed to the drugs received as a part of a regimen received a lower score on the naranjo 's algorithm . the documented adrs are mainly affecting the gastrointestinal tract , bone marrow and skin and this study also pointed out the same . the study of shamna et al . and astolfi et al . also found the predominance of the gastrointestinal system followed by the skin in adr occurrence . cancer chemotherapy damages rapidly dividing cells of bone marrow resulting in myelosuppression thus affecting white blood cells , platelets , and red blood cells . this myelosuppression leads to a lowering of immunity and thus patients on cancer chemotherapy are at a high risk for developing various infections . nausea and vomiting are prominent with most cytotoxic agents and is caused mainly due to direct stimulation of chemoreceptor trigger zone . the documented taxanes adrs are mainly alopecia , anemia , peripheral neuropathy , arthralgia / myalgia , nausea , diarrhea , neutropenia , flushing , rash , thrombocytopenia , and severe hypersensitivity reactions and this study also pointed out the same . since patients in this study received the standard dose , there was no report of these adverse effects . the frequency of candidiasis reported is more in this study as the majority of the patients were receiving repeated cycles of chemotherapy infusion . hyperuricemia and symptomatic hyponatremia were  not predictable ;  though there are some reports of it , which can not be considered conclusive . the documented adrs among vinca alkaloids are alopecia , peripheral neuropathy , constipation , obstipation , abdominal cramps , vomiting , diarrhea , paralytic ileus , urinary retention , polyuria , dysuria , syndrome of inappropriate antidiuretic hormone secretion ( siadh ) , weight loss , fever , stomatitis , headache and optic atrophy with blindness , and this study pointed out the same . hyperuricemia and siadh occur during active cell lysis of highly proliferative tumors of massive burden ( e.g. , leukemia and lymphoma ) by cytotoxic chemotherapy . obstipation is a severe form of constipation associated with fecal impaction and intense abdominal pain . however , as per a study by astolfi et al . lung cancer , cervical and breast cancer were found to be the most common . vincas by binding to intracellular microtubules causes intracellular edema of sensory axons and dose - dependent peripheral neuropathy . whereas taxanes by creating leaky axonal membranes are ultimately neurotoxic to schwann cells , clinically pictured as peripheral neuropathy . paclitaxel was the most commonly used drug among taxanes and vincristine among vinca alkaloids in the inpatient settings and hence the higher incidence of adrs reported with this drug . nausea , vomiting , and hypersensitivity reactions were not observed in this study due to the use of adequate premedication with parenteral dexamethasone , ranitidine and ondansetron and diphenhydramine , respectively . analysis of the type of reported adrs according to rawlin and thompson revealed type a predominance . this result is in line with the study conducted by bates et al . and lazarou et al . , but in another study by suthar and desai , all the reported reactions were type b reactions . type a reactions are dose related and thus were preventable from their known pharmacology and therefore all of them were potentially avoidable . type b reactions comprise approximately 1015% of all adrs and include hypersensitivity drug reactions . with adequate premedication , common adrs such as nausea , vomiting , glossitis , and candidiasis can be effectively controlled . the incidence of definitely preventable reactions reveals the failure of rational drug use in the hospital . this brings out the need for the treating physician to anticipate and counsel the patient adequately before starting of therapy . most of the reactions were of mild to moderate severity and did not warrant stoppage or changing of drug considering the risk - benefit ratio in specific patients . even though most of them were mild reactions , they resulted in an increased health care cost due to an increased length of stay and need of some medical interventions . while severe reactions were more followed by moderate in a study by oshikoya et al . similar studies may be used to identify iatrogenic adverse effects and may help in preventing such occurrences in the future . in this study , most of the reactions showed a similar causality assessment by both the who causality assessment scale and naranjo 's algorithm except for diarrhea and anemia , which were assessed as possible  with lower level of causality by the who scale , were judged as  probable  with higher level of causality by naranjo 's algorithm . certain  reactions as re - challenge was not attempted in any of the patients although some events like neutropenia recurred in the successive cycles of cancer chemotherapy . contradict the study by oshikoya et al . which reported more number of definite reactions . this study provided basic information regarding the safety profile of microtubule - damaging anticancer drugs in a variety of cancers . similar studies have been done which focused on either multiple drugs used in one field of medicine or only on the causality aspect . to the best of our knowledge , a major limitation of the study is that only one case of alopecia and no case of thrombophlebitis reported though being a very common adverse effect with anticancer medications , there are chances of under - reporting and incomplete documentation of data regarding adrs in the case records . the fact that all patients were not admitted following the infusion may have led to missing some adrs , particularly mild ones . nevertheless , early detection of these adrs may help in minimizing the damage by either modifying the dose or changing the offending agent . there is a great need to set up an effective adr monitoring and reporting system in all hospitals and also create awareness among healthcare professionals regarding the importance of this system .