Presented By

RAJEEV PAI
NAPROD LIFE SCIENCE
INDIA
EXECUTIVE SUMMARY :
•GLOBAL AND INDIAN PREVALENCE OF CANCERS
•TODAYS TREATMENT OPTIONS
•AFFORDABLE CHEMOTHERAPHY : PRACTICALITY IN RECENT PRACTICE
•PAIN MANAGEMENT IN CANCER : NEW TREATMENT ERA
 GLOBAL CANCER

Market Size: 65 billion USD

Growth Rate: 23%
Third biggest therapy class
Out of 82 blockbuster drugs
7 are anticancer*

*MabThera, Glivec, Eloxatin, Gemzar, Casodex, Taxotere & Zometa

Source: Business Wire – , 2008 – IMS Health

 CANCER INCIDENCE GLOBALLY

Cancer Incidence
18.30%17.90%
14.60%
12.20%11.50%

5.50% 5.20%
3.60% 3.40%
2.30% 2.20% 1.80% 1.60%

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 TOP 5 CANCERS GLOBALLY BY GENDER

TOP 5 IN FEMALES

Breast 36.70%

Large Bowel 17.30%

Melanoma of
Skin 11.40%

TOP 5 IN MALES Lung 8.90%

Non Hodgkins
Prostate 29.20% Lymphoma 0.10%

Large Bowel 18.50%

Lung 14.10%

Melanoma of
Skin 12.90%

Non Hodgkins
Lymphoma 4.90%
UNIQUE THERAPHY BEHAVIOUR
50% of growth is driven by New Drugs
ž SURGERY ADJUVANT

ž CHEMOTHERAPHY NEOADJUVANT

ž RADIATION THERAPHY

ž HORMONAL THERAPHYS

ž IMMUNOLOGICAL THERAPHY

ž GENE THERAPHY

ž SUPPORTIVE THERAPHY PAIN MANAGEMENT

CANCER TRATMENT OPTIONS

CHF 87 billion = USD 75 billion

The Looming Threat Of The Killer…

…in India
 INDIA-CANCER INCIDENCE AMONG MALES

Leuka.&Lympho.
Others
4%
4%
Tongue
Oesophagus Lung 3%
11% 18% Breast
Oesophagus
27%
Larynx 7%
8%
GI Tract
Mouth 4%
Others
10%
6% Lung
4%
Brain
5% Tongue Thyroid
U.Baldder 9% 6%
5%
Prostate Stomach Mouth
7% Lymphoma Leukaemia 10% 6%
6% 5%
Ovary Cervix
7% 28%

Source: Current Science, Vol. 86, No.4, Feb 2009: Age-adjusted (world population) incidence rates (AAR) per 100,000
males of 10 leading cancers in India
A PRACTICAL CONTEMPORARY APPROACH
 Block microtubule assembly Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine)
Block microtubule disassembly Taxanes (Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) · Epothilones (Ixabepilone)
dihydrofolate reductase inhibitor (Aminopterin, Methotrexate, Pemetrexed) · thymidylate
Folic acid
synthase inhibitor (Raltitrexed, Pemetrexed)
adenosine deaminase inhibitor (Pentostatin)

Purine halogenated/ribonucleotide reductase inhibitors (Cladribine, Clofarabine, Fludarabine)

DNA precursors/ thiopurine (Thioguanine, Mercaptopurine)

antimetabolites thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur, Carmofur, Floxuridine)
(S phase)
DNA polymerase inhibitor (Cytarabine)
Pyrimidine
ribonucleotide reductase inhibitor (Gemcitabine)

hypomethylating agent (Azacitidine, Decitabine)

Deoxyribonucleotide ribonucleotide reductase inhibitor (Hydroxyurea)
I Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan)
Topoisomerase inhibitors II Podophyllum (Etoposide, Teniposide)
(S phase) Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin,
II+Intercalation
Pirarubicin, Valrubicin, Zorubicin) · Anthracenediones (Mitoxantrone, Pixantrone)
Nitrogen mustards: Mechlorethamine · Cyclophosphamide (Ifosfamide, Trofosfamide) ·
Chlorambucil (Melphalan, Prednimustine) · Bendamustine · Uramustine · Estramustine

Crosslinking of DNA Nitrosoureas: Carmustine · Lomustine (Semustine) · Fotemustine · Nimustine · Ranimustine ·

Alkylating
(CCNS) Streptozocin

Alkyl sulfonates: Busulfan (Mannosulfan, Treosulfan)

 dihydrofolate reductase inhibitor (Aminopterin, Methotrexate,
Folic acid Pemetrexed) · thymidylate synthase inhibitor (Raltitrexed,
Pemetrexed)
adenosine deaminase inhibitor (Pentostatin)

halogenated/ribonucleotide reductase inhibitors (Cladribine,

Purine
Clofarabine, Fludarabine)
DNA precursors/ thiopurine (Thioguanine, Mercaptopurine)
antimetabolites
(S phase) thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur,
Carmofur, Floxuridine)

DNA polymerase inhibitor (Cytarabine)

Pyrimidine
DNA replication ribonucleotide reductase inhibitor (Gemcitabine)
inhibitor
hypomethylating agent (Azacitidine, Decitabine)
Deoxyribonucleotideribonucleotide reductase inhibitor (Hydroxyurea)
Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan,
I
Belotecan)
Topoisomerase inhibitors II Podophyllum (Etoposide, Teniposide)
(S phase) Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin,
II+Intercalation Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) ·
Anthracenediones (Mitoxantrone, Pixantrone)
Nitrogen mustards: Mechlorethamine · Cyclophosphamide (Ifosfamide,
Trofosfamide) · Chlorambucil (Melphalan, Prednimustine) ·
Crosslinking of DNA
Alkylating Bendamustine · Uramustine · Estramustine
(CCNS)
Nitrosoureas: Carmustine · Lomustine (Semustine) · Fotemustine ·
CA BREAST
ž FAC: CYCLOPHOSPHAMIDE + DOXORUBICIN + 5FU
ž CMF: CYCLOPHOS + METHOTRXATE + 5FU
ž AC : DOXO + CYCLOPHOS

PRIMARY THERAPHY
COST : AFFORDABLE

ž PACLI + DOCE + VINORELBINE

ADVANCE THERAPHY
COST : HIGHER

HAND BOOK OF CANCER CHEMOTHERAPHY, 5TH EDI,2009, RONALD SKEEL

HEAD AND NECK CANCER
ž CISPLATIN + 5FU
ADVANCE STAGE WITH NO PRIOR TEATMENT
COST: AFFORDABLE

ž METHOTREXATE+ PACLITAXEL
COMBINATION COTRAINDICATED PRIOR TREATMENT
COST: CAN BE AFFORDABLE

ž DOCETAXEL + CISPLATIN + 5FU

PRIOR TREATED PATIENT
COST : HIGHER

HAND BOOK OF CANCER CHEMOTHERAPHY, 5TH EDI,2009, RONALD SKEEL

NSCLC
ž CISPLATIN + PACLI
ž CISPLATIN + VINORELBINE
ž CISPLATIN + PACLI
ž CISPLATIN + GEMCITABINE
ž CISPLATIN + DOCE
ž GEFTINIB AS MPNOTHERAPHY
ž PEMETREXATE AS 1ST LINE

WIDE RANGE OF OPTIONS

HAND BOOK OF CANCER CHEMOTHERAPHY, 5TH EDI,2009, RONALD SKEEL

 Docetaxel/capecitabine versus Doxorubicin/cyclophosphamide

Sr.no. Features Molecule

Capecitabine / Doxorubicin Benefit Reference
In St. II/III breast cancer Docetaxel /cyclophosphamide
More PMID:
1 Clinical response rates 84% 65%
improvement 12897327
2 Nausea and vomiting Very less More Better life PubMed -
indexed for
Tumor pathologic
3 21% 10% Longer life MEDLINE
complete response
PROTOCOL NAPROD’s COST MNC COST*)
CMF 6 USD 14 USD
CAF 20 USD 42 USD
CEF 50 USD 90 USD
PACLI + CARBO 100 USD 300 USD
GEMCI + CARBO 85 USD 210 USD
DOCE + CISP 120 USD 1500 USD

*). Innovator’s Cost

ž COST OF CHEMOTHERAPHY IS RELATED TO STAGE OF CANCER
ž IF DETECTED EARLY COST OF TREATMENT CAN BE MINIMISED
ž WIDE RANGE OF PROTOCOLS ARE HELPFUL TO REDUSE THE COST
OF THERAPHY
ž WELL EQUIPPED MANUFACTURER LIKE NAPROD CAN AFFORD TO
OFFER COST EFFECTIVE CHEMOTHERAPY
ž SMALLER MOLECULE LIKE 5FU,ETOPOSIDE, METHOTREXATE,
DOXORUBICINE CAN STILL DO WONDERS AND REDUSE COST OF
THERAPHY IF USED LOGICALL Y.
ž IF CHEMOTHERAPHY AGENTS ARE DISTRIBUTED THROUGH GOVT
OR SEMI GOVT ORGANOZATION , FAKE DRUG INFILTRATION AND
POOR RESPONSE CONTROL CAN SAVE LOTS OF MONEY
AN OVERVIEW
ž Our ability to allow the patient to rehabilitate without
pain offers the patient a chance to regain strength and
function and to expend physical and mental energy on
recovery and restoration of life.

A multidisciplinary approach to cancer pain is crucial.

One needs to look for the culprits believed to be
responsible for the pain symptoms and then treat these
causes with an open mind and the appropriate tools.
We have a wide variety of skills to offer patients and
should do so in a manner that is consistent with each
individual patient’s goals.
Pain associated with cancer may be a result of tumour pressure in
70% to 80% of patients or anticancer treatment in 15-19% patients
or it may be unrelated to cancer and treatment (3-5%).

Pain in cancer can be grouped into four causal categories:

ž Cancer itself , e.g. soft tissue, visceral, bone,

neuropathic, metastatic
ž Treatment related, e.g. chemotherapy –
related mucositis, postoperative syndromes,
radiation induced
ž Debility, e.g. constipation, muscle spasm /
tension
ž Concurrent disorder, e.g.spondylosis, osteoarthr itis.
ž The World Health Organization (WHO) has described a 3-step
analgesic ladder as a framework for pain management. This ladder
has been shown to provide adequate analgesia to 90% of cancer
patients and more than 75%of the terminally ill cancer patients.
ž It involves a step approach based on the severity of pain. If the pain is
mild (pain score 1-4), one may begin with prescribing step 1
analgesics, such as NSAIDs (nonsteroidal anti-inflammatory drugs). If
pain persists or worsens (mild to moderate pain, pain score 5-6), step
2 analgesics such as weak opioids are indicated. If still pains
uncontrolled (moderate to severe pain, pain score 7-10), strong
opioids such as morphine, hydromorphone, fentanyl should be
started.
ž The fourth step includes use of nerve blocks, spinal (epidural and
subarachnoid) administration of local anaesthetics, opioids, •2
agonists, spinal cord stimulation, and surgical interventions,
vertebroplasty, radiofrequency ablation as dictated by patient
condition.
ž OPIOIDS :
A series of case report have demonstrated the clinical problems of
inadequate pain control with escalating opioids doses in the
presence of dose limiting toxic effects including hallucination,
confusion, hyperalgesia, myoclonus, sedation and nausea. These
problems can be managed by switching to an alternative opioid
with result being improved pain management and decreased toxic
effects.
ž Transdermal fentanyl patches currently available are formulated
to provide analgesia lasting up to 72 hours.
ž Side effects are consistent with other opioid therapies, including
sedation, constipation and nausea.

Galer BS, Coyle N, Pasternak GW et al. Individual variability in response to different opioids: report of 5 cases. Pain
2008;49(1):87-91.
ž ADJUVANT DRUGS :
Commonly used adjuvant drugs are antidepressant, corticosteroid,
and local anaesthetic. Other agents used for specific conditions
e.g. bisphosphonates for bone metastasis, baclofen for spastic
pain, clonidine, gabapentine, ketamine for neuropathic pain.

ž NEUROLYTIC NEURAL BLOCKADE:

Neurolytic blocks are used to interrupt the pain pathways. These are
useful in the control of intractable visceral cancer pain. Neurolysis
is typically achieved chemically using injection of alcohol (50-
100%) or phenol (7-12%).
ž When used with opioids, neurolytic blocks allow opioid doses to
be reduced, resulting in fewer side effects associated with
opioids.
ž INTRASPINAL ANALGESICS:
Morphine is the only opioid approved by US Food and Drug Administration
(FDA) for the treatment of cancer pain via intraspinal administration; however,
other opioids are commonly used including hydromorphone, fentanyl, and
sufentanil.
ž Currently, the nonopioid agents that are most commonly used in the
management of cancer pain are clonidine and bupivacaine Ziconotide, a
calcium channel blocker, has been evaluated for the treatment of severe
chronic pain in patients who either cannot achieve adequately controlled pain
with systemic opioids or who are intolerant to systemic opioids.
ž In the future spinal opioids and novel nonopioid drugs will likely play an
important role in pain management as a mainstay of diverse analgesic
therapies combination spinal analgesia is the subject of a current systematic
review.

Staats PS, Yearwood T, and Charapata SG, et al.Intrathecal ziconotide in the treatment of refractorypain in patients with cancer or AIDS: a
randomized controlled trial JAMA 2008;291:291:63-70.
ž SPINAL CORD STIMULATION:

Spinal Cord Stimulation is a means where by the pain is blocked from

effectively reaching the brain by interference with the spinal
transmission of certain pain signals. Spinal Cord Stimulation (SCS)
does not block all signals, and thus, leave the ability to feel certain
pain signals that are protective. The mechanism of analgesia
produced by SCS is still unclear. Some hypothesis involve antidromic
activation of central inhibitory mechanisms, increase in substance –P
release, and actual block of transmission of electrochemical
information anywhere in the dorsal spinothalamic tract.

ž 20-80% of patients experience long term analgesia from SCS.

Rich Payne and Gilbert RG et al. Management of pain. In: Derek Doyle, Geoffrey Hanks, Nathan Cherny and Kennanth Calman (eds). Oxford
Text Book of Palliative medicine (4rth ed) New York: Oxford University Press 2007:288-458.
ž VERTEBROPLASTY

ž SURGICAL ANALGESIC TECHNIQUES

ž RADIOFREQUENCY ABLATION

ž NEUROSTIMULATORY PROCEDURES

ž ANTINEOPLASTIC INTERVENTIONS

ž RADIOTHERAPY:

CONCLUSION :
ž Most patients with cancer pain can achieve adequate analgesia with
conventional oral pharmacological therapy and opioid and
nonopioid analgesic therapy remains the cornerstone of cancer pain
management. Nevertheless, chronic cancer pain can be
psychologically devastating because it is a constant reminder of the
incurable and progressive nature of the disease; therefore, all
available measures appropriate to the patient should be explored.
THANK YOU