1 MED II 6 - Systemic Therapy In Cancer.pdf

November 10, 2017 | Author: Dia Dimayuga | Category: Chemotherapy, Cancer, Radiation Therapy, Apoptosis, Lymphoma
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Medicine II: 1.6

Dr. Gracieux Fernando June 27, 2014



mastectomy followed by radiation, were practically the same for all procedures. The only difference between the two was that patients with node- positive disease tended to have a poor prognosis compared to node negative disease.

I. History of Cancer II. Treatment Modalities III. Cytotoxic Chemotherapy IV. Pharmacologic Aspects V. Fractional Cell- Kill Hypothesis VI. Skipper and Scable Principle VII. Resistance to Anti- Cancer Agents VIII. Causes of Resistance IX. Combination Therapy X. Indications of Chemotherapy XI. Types of Responses to Chemotherapy XII. Response Evaluation of Chemotherapy in Solid Tumors XIII. Calculating the Sum of the Longest Lesion XIV. Tumor Response to Chemotherapy XV. Contraindications to Chemotherapy XVI. Hormonal Therapy in Cancer XVII. Immunotherapy in Cancer XVIII. Targeted Therapy XIX. Side Effects of Immunotherapy

Figure 1. Distant disease- free survival (left) and overall survival (right) 

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HISTORY OF CANCER Remote sympathy: Most accepted approach to treating cancer from 200 BC to middle ages o First report of malignancy o Galen’s Humoral Theory of Disease: malignancy is a systemic disease and so there was no attempt to treat the malignancies locally o Cancer patients at that time were left best on their own because they had a very poor understanding of what the disease is all about. Andreas Vesalius: Performed anatomical dissections and revealed that there was no basis for Galen’s Humoral Theory. th 15 century: Localized management of malignancies through surgery was considered, but actual success was achieved when the practices of anesthesia and antisepsis were established. Late 1800s: Surgery as a treatment modality for malignancies had become the standard, but recurrences were common. William Stewart Halsted: played a prominent role in the surgical management of malignancies, especially those of the breast o He observed that the most common way that a tumor could recur is when it would grow back particularly at the site where it was first removed. o Theorized that the reason for recurrence was due to inadequacy of the surgical procedure. o Proposed solution was to perform more surgeries or extend the field of surgery, such as resection of the breast, pectoralis major and minor, and the entire content of the axillary components in breast cancer. o Halsted’s radical mastectomy – named after him Halsted’s subsequent colleagues took the concept of radical mastectomy to its logical limits and created procedures such as extended radical mastectomy (clavicle was taken out and the chest opened up to reach the internal mammary chain of nodes), and the ultra-radical mastectomy (dissection reached the neck). During those times, dissecting and removing as much viable and potential tissue as possible was the solution for malignancy. THE NEED FOR SYSTEMIC THERAPY Years later, physicians compared results of various surgical techniques to check for survival improvements or recurrence improvements. It was noted that recurrence rates and survival rates among those who underwent a radical mastectomy, a simple mastectomy and a

Rudolf Virchow: Proposed the cellular concept of disease and concluded that there are only two ways in which cell increases their size which is through hypertrophy or hyperplasia. o He realized that malignant cells are cells with a disorganized growth potential, and they acted as if they had a life of their own. Since this was something that he had not seen before, he called it neoplasia. He concluded that the main cellular characteristic of malignancies was continuous proliferation. Edward and Hellen Kumar: Pathologists who studied deaths caused by mustard gas, which was invented during World War I. They discovered one innate characteristic in many patients who have been exposed: bone marrow aplasia. This suggested that the gas acted on tissues with rapid proliferation. Louis Goodman and Albert Gilman: Pharmacologists from Yale University who were sent to study the toxic effects of mustard gas exposure during World War II. o They concluded that mustard gas is a vesicant in its gaseous forms, and that it actually causes severe damage to the pulmonary system leading to death. In order to remove the vesicant effects, they gave it via IV to experimental animals, and they noted that although there were no vesicant effects, bone marrow aplasia was replicated. o They returned to Yale University and convinced a thoracic surgeon colleague to put a patient with lymphoma through a 10-day infusion of nitrogen mustard via IV. Complete regression of the lymphoma was noted after the treatment, and it became the first successfully documented system therapy for a solid malignancy. Today, nitrogen mustard is used under the name Mechlorethamine and is still used as a treatment option for patients with Hodgkin’s lymphoma.

TREATMENT MODALITIES Systemic modalities: 1. Cytotoxic chemotherapy- the most common systemic therapy 2. Hormonal therapy 3. Biologic therapy  Immunologic therapy  Targeted therapy  Gene Therapy Today, molecular targeted therapies are also being used.


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MEDICINE II 1.6    

CYTOTOXIC CHEMOTHERAPY Effectiveness is primarily on cell multiplication and tumor growth Most agents affect macromolecular synthesis and function (DNA, RNA, proteins) Agents are classified roughly on their activities relative to the cell generation cycle Cytotoxic chemotherapy targets DNA replication. Most of them would have their activity within the cell cycle and are capable of hitting mostly cells that are in active proliferation

SITES OF ACTION OF CYTOTOXIC AGENTS The figure shows an example of the general family or classification of chemotherapeutic agents and the sites of actions in relation to the cell cycle.

Figure 3. Sites of action of cytotoxic agents at the cell cycle level.   Figure 2. The cell cycle



MECHANISMS OF DRUG ACTIVITY Phase non- specific – drugs would be active in any phase of the cell cycle A. Cycle non- specific drugs - drugs that can be active whether the cell is replicating of not EXAMPLES:  Nitrosoureas family (BCNU, CCNU and CDNU) and Methazolamide-- Both are used for the treatment of CNS tumors  Corticosteriods (Prednisone, dexamethasone and prednisolone)—used for hematopoietic malignancies B. Cycle specific drugs – drugs that are only active if the cell is anywhere within the cell cycle; increased dose=increased efficacy EXAMPLES:  Alkylating agents (Cyclophosphamide, thiphosphamide) and platinum analogs (Cisplatin, carboplatin)—Full cycle specific (can act on any phase of the cycle)  Tumor antibiotics (Doxorubicin and epirubicin)-- Cycle specific but have the greatest activity in the S phase of the cell cycle Phase specific – drugs that are cycle specific- phase specific  IMPLICATIONS: o Limited to a single- exposure cell kill. Phase- specific agents given as a single dose, will only kill cells that are in that phase of the cell cycle. This is why they are considered to have a limited cell- kill potential. o Increasing cell- kill by prolonged exposure and recruitment. Prolonging the infusion rate of a cycle-specific phase-specific agent is the best way to improve its efficacy. This will allow the other cells to enter into the phase of the cell cycle that is sensitive to the agent, eventually destroying them.  EXAMPLES: o 5- FU A pyrimidine analog and S- phase specific agent o Since it is an S- phase specific agent, it is not given as a single bolus dose when treating colon cancer. It is most effectively used either as a 5-day continuous bolus injection or a weekly continuous injection. It can also be given as a 28-day continuous intravenous infusion.

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Alkylating agents are effective in the entire cell cycle Antibiotics are cycle- specific although they have a preferential activity in the S- phase Antimetabolites are cycle- specific for the S- phase of the cell cycle because they act as analogs of the backbones of DNA Vinca alkaloids and taxanes are effective in the M- phase of the cell cycle because they attack the mitotic spindle


PHARMACOLOGIC ASPECTS Absorption  Determines route of administration  Majority are deactivated by gastric acid and are fully absorbed in the GIT so majority of the agents are given via IV, although some agents like 5-FU already have oral analogs that are used in the clinics.


Area of Distribution  Determines the compartments in the body where the agents are going to be active  Since they are macromolecules, it will be difficult for them to traverse certain barriers particularly the blood brain barrier. Because of that, the CNS can become a potential site of malignancy recurrence.


Biotransformation  Many of these agents are actually utilized as pro- drugs and will require certain enzymes of the body to convert them into the active metabolites.  These enzymes are mainly located in the liver, and in cases of hepatic insufficiency, there can be decreased conversion to an active agent resulting to low plasma levels of the drugs.


Drug Dosing  For cancer patients, the computation for the dose of these chemotherapeutic agents is largely based on the total body surface area, due to their toxicity and their narrow profile of toxicity vs therapeutic range.


Excretion  Determines need for dosage adjustment in the presence of organ insufficiency  Many of these drugs are demetabolized or metabolized eventually by the liver and many of them are excreted by the renal system. The presence of hepatic or renal insufficiency is going to require


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MEDICINE II 1.6 dosage adjustment otherwise there will be prolonged half- life leading to higher potential for toxicity.

FRACTIONAL CELL- KILL HYPOTHESIS: 3 LOG- KILL- 1 LOG REGROWTH PRINCIPLE  Fractional cell - kill Hypothesis: states that every cycle of chemotherapy will kill the same fraction of cancer cells. Also known as the 3- log kill, 1 log regrowth principle. 10 3  In a tumor with 10 cells, a cycle of chemotherapy will result in 10 (3 7 log kill) cells dying and 10 cells remaining. During recovery, tumor is 1 2 expected to grow by 10 (1 log regrowth). Net cell kill per course is 10 .

TUMOR GROWTH The fractional cell-kill hypothesis makes the wrong assumption that in a tumor, all the cells are proliferating. However, this is not the case. There are phases in the cell cycle where there is practically zero growth potential, such as in a clinically apparent tumor in the plateau phase of the Gompertzian growth.

Figure 5. Gompertzian growth. 

Figure 4. 3-log kill, 1 log regrowth principle.  

It is estimated mathematically that in 1 chemotherapeutic cycle, 99.9% of cancer cells are killed. So, if one cycle can already kill 99.9% of cancer cells, why is there a need for 4-6 cycles? 10 In a hypothetical patient with 10 number of cells at baseline, one cycle 10 of chemotherapy would leave him with 0.1% tumor cells. 0.1% of 10 or 10 -3 7 10 x 10 equals 10 , which is still a very large number. This is the reason why patients have to undergo 4-6 cycles of chemotherapy. Chemotherapy cannot be given consecutively because it is a very toxic procedure. On the average, a 3-week interval is given before the patient can actually receive the next cycle of chemotherapy to allow for bone marrow recovery. It is also estimated that when the patient recovers from the side effects, the tumor also recovers by a factor of 1 log. So the net decrease in the tumor cells after one cycle is 2 logs (3 logs to kill, 1 log to regrow). To decrease the number of tumor cells to a point where the patient’s own immune system can handle them, which is only about 1000 tumor cells, 4 cycles of chemotherapy is needed. Usually, when a test response th is gotten at the 4 cycle, an additional 2 cycles of chemotherapy is given to consolidate the response. This is why on the average, cancer patients receive about 4-6 cycles of chemotherapy.

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 CLINICAL IMPLICATIONS OF THE FRACTIONAL CELL- KILL HYPOTHESIS  Chemotherapy cycles must be given on time. o With 1 log of regrowth after every cycle, a delay in the treatment could mean more regrowth or probable return to baseline, wasting the effects of the initial cycle. o To have an effective chemotherapy cycle, it should be emphasized that patients must receive it on a strict schedule.  One cycle will be ineffective in providing any type of relief to the cancer patient. The implication of the Fractional Cell- Kill Hypothesis is that treatments have to be planned, and that to be effective, chemotherapy must be completed.


The problem here is that, in a clinically apparent tumor where, most of the cells are no longer proliferating, can chemotherapy still be utilized especially if there is already metastasis? This can be explained by the Skipper and Scable Principle. SKIPPER AND SCABLE PRINCIPLE Growth fractions and doubling times may differ from cells in the primary site versus those in micro- metastases Magnitude of response in plateau phase of the Gompertzian growth need not reflect the response of micro- metastases in exponential growth st 1 order kinetics relative to cell kill by cytotoxic agents apply to those cells with constant growth fraction in exponential growth Ablation of primary tumor with a resultant decrease in total tumor cell burden may alter the growth characteristics of residual micrometastases Primary site: crowded, with lots of competition for nutrients, plateau phase in Gompertzian growth is usually in order Micro-metastasis: cells that escaped the primary site and are already in logarithmic growth, but still undetectable The Skipper and Scable Principle differentiates the growth potentials of cells that are in the primary site, and cells in micro-metastases When a tumor is in the Gompertzian plateau phase, the number of proliferating cells is equal to number of dying cells/cells not proliferating resulting to a growth potential of zero. This is why chemotherapy can still be given in very large tumors, as there are still proliferating cells present. This is the concept of induction chemotherapy. In patients with locally advanced diseases, such as a 10 cm breast cancer with metastasis of the skin involving majority of the axillary nodes, chemotherapy is given prior to surgery to decrease the size of the tumor, and in so doing, lessen the extent of surgery performed. Once surgery is done, chemotherapy can be resumed to target the remaining cells. RESISTANCE TO ANTI- CANCER AGENTS Natural Resistance  Initial non- responsiveness of a tumor to a given drug  Tumors which are naturally resistant probably express substances that render them naturally immune to the effects of chemotherapy or because their growth potential is very slow. An example is thyroid carcinoma  Chemotherapy plays a very poor role in naturally resistant tumors.


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Acquired Resistance Unresponsiveness to certain drugs that emerge after initial successful treatment  In acquired resistance, the patient is exposed to the drug. The patient initially responds to the drug but subsequent use of the drugs renders the tumors unresponsive  Once acquired resistance occurs, it sometime extends to several member of the same family of drugs. 


Mechanism: o Effects are due to different growth fractions in the tumor’s Gompertzian growth curve. o Goldie-Coldman Hypothesis: As a tumor cell population increases, there is an ever expanding number of drug-resistant phenotypic variants which arise due to somatic mutations that become difficult to eradicate. Initially good response since all of the sensitive cells are killed  remission because all that is left are the mutated cells that developed resistance. Overcoming resistance from cell kinetics o Reduce tumor bulk with loco-regional modalities (surgery, RT) o BIG TUMOR MASS debulk  smaller mass cells left rapidly proliferating  sensitive to chemotherapy o Use combinations that include drugs that can affect resting populations. o EXAMPLE:  CHOP chemotherapy regimen frontline treatment for nonHodgkin’s lymphoma)  Cyclophosphamide (alkylating agent) – cycle specific, hits proliferating cells  H-Adriamycin – cycle specific, hits cells in the S-phase  Oncovin (Vincristine) – hits cells in the M phase  Prednisone – cycle non-specific; hits resting cells o Schedule drugs to prevent phase escape or to synchronize cell populations and increase cell kill. 2. BIOCHEMICAL CAUSES Mechanism o Inability of tumor to convert drug to active form o Many of these drugs are prodrugs, and patients with deficiencies in enzymes that can convert these drugs to active agents, or patients with hepatic insufficiency may have problems with maintaining adequate plasma levels of these drugs giving the tumor some form of resistance. [3] o Presence of substances that may overcome a potential lethal blockade. o EXAMPLE:  Increased expression of BCL2 which is an anti-apoptotic, so even if p53 cells express proteins like BAX, BAD and BID which are pro-apoptotic, no apoptosis is going to occur  Total loss of P53 function: nothing triggers apoptotic process  Multi drug resistance through p-glycoprotein expression (glycoprotein is an active transmembrane cytoplasmic pump)  ATP-mediated mechanism: Due to MDR p-glycoprotein expression, the cell pumps the drug out of the cell drug does not reach the nucleus no chemotherapeutic effect  tumor resistance to the particular drug



Figure 6. Active Pump of the MDR gene Overcoming biochemical causes of resistance o Use combination chemotherapy: Hits different populations of cells o Use biologic response modifiers: o EXAMPLE:  Folinic Acid used in conjunction with 5-FU  improves affinity of 5-FU with its target enzyme thymidilate synthase ; used in colon CA patients 3 ways to improve response by increasing dose w/o risk of toxicity: nd o Use a 2 agent to rescue normal cells :  Folinic Acid in conjunction with Methotrexate(purine analog)  Methotrexate targets Dihydrofolate reductase ↓ amt of folate for DNA synthesis  prevents the effects of high dose Methotrexate, such as in fulminant renal toxicity and failure  In osteosarcoma  give Methotrexate at high dose (20g) 24 hrs after give Folinic acid to replenish normal cells toxicity avoided o Follow marrow-lethal doses of chemotherapy with autologous bone marrow transplantation (eg leukaemia, multiple myeloma, relapselymphoma) o Combine high dose chemotherapy with blood cell regrowth factors (e.g. F-CSF, GM-CSF). Used to overcome the problem of bone marrow depression which comes with administering high doses of chemotherapy. 3. PHARMACOLOGICAL CAUSES Mechanism: o True resistance does not exist: Tumor is sensitive to drug, but drug has below optimal plasma level  Poor or erratic absorption  Increased excretion or catabolism:  Ex. Fast acetylators  metabolize drugs much faster lower plasma levels and lower efficacy  Drug Interaction:  Ex. TCAs, anticonvulsants, some corticosteroid increase the activity of the cytochrome 450 enzyme systems  increase the metabolisms of certain agents their plasma levels again fall lower drug efficacy  Sometimes, the drug itself can increase its own metabolism:  Ex. Ifosfamide (alkylating agent) if given beyond a certain duration, it starts to metabolize itself; now, it is given in a shorter infusion time (2-4 hour)  Imatinib 6-8 months lower response; increase dose at time of resistance. o True pharmacological resistance:  Poor transport of tumor cell lymphomas: sites that cannot be reached by drugs particularly CNS and testes (sanctuary sites for high grade tumors such as leukemia and lymphoma)

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MEDICINE II 1.6 COMBINATION THERAPY ADVANTAGES  Prevention of resistant clones Cytotoxicity to resting and dividing cells  Biochemical enhancement or effect: Synergistic  Sanctuary access: Examples are the CNS and the testis  Rescue: One agent is combined with another to rescue the patient from the toxic effects of the first agent 

AIM OF COMBINATION CHEMOTHERAPY The aim of the combination is to achieve a balance. There must be efficacy combined with safety, less toxicity in the patient.

Neo-adjuvant (Induction Chemotherapy): Chemotherapy given prior to surgery prevent metastases and decrease tumor size (to facilitate a less debilitating or less disfiguring type of surgery e.g. breast cancer o Osteosarcomas – Usually affect young individuals, teenagers; affects extremities (proximal tibia, distal femur) leading to amputation (only surgery for osteosarcoma). Neo-adjuvant chemotherapy will decrease tumor size then do limb sparing operation, hence no need for amputation. Remove the tumor and the affected bone then do reconstructive surgery on functional [3] extremity; increases survival Concurrent Chemotherapy – Used at the same time with radiotherapy. Chemotherapy is a good radiosensitizer increases the tumor’s sensitivity to the effect of radiotherapy. Ex. Neck malignancies, late stage lung cancer Salvage Chemotherapy - Failed the first treatment. But there are subsequent treatments that may create a complete response. Ex. NonHodgkin’s lymphomas

Figure 7. Aim of combination therapy. The concept of maintaining that balance is very important because the margin between the therapeutic efficacy dose and toxic dose of a chemotherapeutic agent is very narrow. For some drugs and some drug combinations, the therapeutic dose is the toxic dose; therefore, if the patient is given a dose that is higher than the computed, there will be better tumor control, but the patient is going to suffer from toxicity. On the other hand, if the dose is lowered to the point that there is no toxicity, there will also be no efficacy and the patient could eventually develop resistance to chemotherapeutic agents.

2. PALLIATIVE CHEMOTHERAPY Objective is not to cure or prolong survival of patients; rather, it aims to control symptoms. When giving palliative chemotherapy, all rules of chemotherapy are broken: o Give single agent rather than a combination: less toxicity, maybe equal efficacy o 6 cycles not completed: initially symptomatic after 3 cycles asymptomatic stop (Why continue? Survival of patient will not improve) TYPES OF RESPONSE TO CHEMOTHERAPY

Figure 9. Complete response. There is disappearance of all clinical, radiologic and biologic signs of the tumor.

Figure 8. Therapeutic effect and toxic effects. 

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A good oncologist knows how to balance between the efficacy of chemotherapeutic agent and the potential toxic side effects. Patients should always be informed that there are always going to be side effects, and that the absence of those could mean that adequate levels of the drug for it to be effective are not achieved. INDICATIONS OF CHEMOTHERAPY 1. CURE CONTROL Primary Chemotherapy: Chemotherapy is the main treatment for a particular tumor e.g. hematologic in origin(lymphoma, leukeaemia), rapidly proliferating, metastatic in early stages (SCLC) Adjuvant Chemotherapy: Chemotherapy given after a surgical procedure to kill micrometastatic disease, which is a cause of treatment failure and recurrence eg breast cancer, colorectal malignancy

Figure 10. Partial response. There is a decrease of the multiple of two tumor diameters by at least 50%.


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MEDICINE II 1.6 o o o

Lymphangitic cutis Cystic lesions Abdominal masses that are not confirmed and followed by imaging techniques Once the lesion has been classified as either measurable or nonmeasurable, target lesions should be determined among the measurable lesions. These will be the baseline lesions, measured at every response of chemotherapy.

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1. TARGET LESION All measurable lesions up to a maximum of 5 lesions per organ and no more than 10 in total Representative of all involved organs Selected based on their longest diameter Used to calculate sum of longest diameter (SLD) at baseline For a patient with several lesions in the lung or liver, a physician will choose the three biggest lesions in the lungs and three biggest lesions in the liver as long it can be measured in one diameter and will use this measurement in calculating the SLD

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2. NON-TARGET LESION All other lesions and non-measurable lesions Not required to be measured

 Figure 11. Stable disease. There is regression in tumor size less than 50% or no change in size from the baseline.

 CALCULATING THE SUM OF THE LONGEST LESION (DIAMETER SLD) Scan Target Baseline Scan SLD Method Lesions Measurements (cm) 1 Spiral CT R lobe liver 2.5 x 1.6 8.8 (2.5 + 3.9 + 2.4) Spiral CT L lobe liver 3.9 x 1.8 3 Spiral CT LLL lung 2.0 x 2.4 # Figure 12. Progressive . There is an increase of the multiple of two tumor diameters by at least 25%. 

The type of response that you would want to see will depend on the endpoints: if you want to: o Cure patient: there should be a complete response o Prolong survival/ palliate symptoms: No response / Stable Disease acceptable o Partial response (good response) o Stable disease (acceptable response because tumor will not grow): contributes to survival; diminishing symptoms  Problem with WHO definitions of response o Requires two dimensions and in many situation it is difficult to get two accurate dimensions o There are metastasis that cannot be measured o Pleural effusion o Multiple bone metastasis o Leptomeningeal metastasis ** Difficult to use and hence has effect on clinical trials

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RESPONSE EVALUATION IN CHEMOTHERAPY IN SOLID TUMORS (RECIST CRITERIA) 1. MEASURABLE LESIONS Lesions that can be accurately measured in at least one dimension with longest diameter (LD) LD ≥ 20 mm with conventional techniques LD ≥ 10 mm with spiral CT 2. NON-MEASURABLE LESIONS

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All other lesions Small lesions that don’t meet measurable criteria Truly non-measurable lesions such as: Bone lesions Leptomeningeal diasease o Ascites o Pleural/ pericardial effusion o Inflammatory breast disease

RECIST CRITERIA: EVALUATION OF TARGET LESIONS Complete Response (CR) Disappearance of ALL target lesions Partial Response (PR) >30% DECREASE in Sum of Longest Diameter (SLD) when compared to baseline SLD Progressive Disease (PD) >20% INCREASE in SLD when compared to smallest SLD since initiation of treatment of appearance of any new lesions Stable Disease (SD) Does not meet criteria for CR, PR or PD EXAMPLE: # 1 2 3

Scan Method

Target Lesions

Spiral CT Spiral CT Spiral CT

R lobe liver L lobe liver LLL lung

Baseline Scan Measurements (cm) 2.5 x 1.6 3.9 x 1.8 2.0 x 2.4


8.8 (2.5 + 3.9 + 2.4)

Measurements after Therapy (cm) 1.0 x 0.8 2.0 x 1.0 1.0 x 1.0


4.0 (1.0 + 2.0 + 1.0)

Overall response = 8.8 - 4.0 = 4.8/8.8 = 0.545 x 100 = 54.5% 54.5% → PARTIAL RESPONSE (>30% decrease in SLD) RECIST CRITERIA: EVALUATION OF NON-TARGET LESIONS Complete Response (CR) Disappearance of ALL non-target lesions Progressive Disease (PD) Persistence of 1 or more non-target lesions without progression Stable Disease (SD) Unequivocal progression of existing nontarget lesions Appearance of one or more new lesions


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MEDICINE II 1.6 Unable to Evaluate (UE)

If a lesion cannot be assessed due to technical reasons (e.g. radiograpg is of poor quality) If a lesion was assessed using a method different from that used at baseline (e.g. pleural effusion assessed by CT as baseline, and CXR at this time point)

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ADVANCED CANCERS POSSIBLY CURABLE BY CHEMOTHERAPY WITH RADIATION THERAPY: Squamous cell carcinoma of the head and neck Breast cancer Cervical cancer Non-small cell lung cancer Stage III Small cell lung cancer

CANCERS POSSIBLY CURED WITH CHEMOTHERAPY AS ADJUVANT AFTER SURGERY:  Breast cancer  Colorectal cancer  Osteosarcoma  Soft tissue sarcoma

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Islet cell neoplasms Breast cancer Colorectal cancer Renal cell cancer

Chemotherapy can adequately control their symptoms and in some cases, can prolong their survival.

RECIST CRITERIA: EVALUATION OF OVERALL RESPONSE New Overall Target Lesions Non-Target Lesions Lesions Response CR CR No CR CR Present No PR PR Non-PD No PR SD Non-PD No SD PD Any Yes or No PD Any PD Yes or No PD Any Any Yes PD TUMOR RESPONSES TO CHEMOTHERAPY CANCERS WITH A POSSIBILITY OF CURE IN THE ADVANCED STAGE:  Acute lymphoid and myeloid leukemias  Hodgkin’s disease  Lymphomas, certain types  Germ cell neoplasms (Embryonal cancer, teratocarcinoma, seminoma or dysgerminoma , choriocarcinoma)  Gestational trophoblastic neoplasms  Pediatric neoplasms (Wilm’s tumor, embryonal rhabdomyosarcoma, Ewing’s sarcoma, Peripheral neuroepithelioma, neuroblastoma)  Small cell lung cancer  Ovarian cancer For adults, lymphoma, ovarian carcinoma, and small cell carcinoma only. Children have a higher chance of cure even at the advanced stage of the disease.

Lymphomas, certain types Multiple myeloma Gastric cancer Cervical cancer

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TUMORS POORLY RESPONSIVE IN THE ADVANCED STAGE TO CHEMOTHERAPY: Pancreatic cancer  Non-small cell lung cancer Biliary tract neoplasms  Prostate cancer Thyroid cancer  Melanoma Carcinoma of the vulva  Hepatocellular carcinoma o o o

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CANCERS POSSIBLY CURED WITH “HIGH DOSE” CHEMOTHERAPY WITH STEM CELL SUPPORT: Relapsed myeloid and lymphoid leukemias Relapsed Hodgkin’s and non-Hodgkin’s lymphomas Chronic myeloid leukemia Multiple myeloma CANCERS RESPONSIVE WITH USEFUL PALLIATION BUT NOT CURABLE BY CHEMOTHERAPY:  Bladder cancer  Endometrial cancer  Chronic myeloid leukemia  Soft tissue sarcomas  Hairy cell leukemia  Head and neck cancers  Chronic lymphocytic leukemia  Adrenocortical carcinoma


Advances in chemotherapy are measured by how many of these tumors are shifted to previous classifications. Renal cell carcinoma used to belong to this group but because of newer treatment modalities, it is now considered palliative. Melanoma is used to be unresponsive to systemic therapy.

CONTRAINDICATIONS TO CHEMOTHERAPY Infection - Patients become leukopenic and cannot fight infection. Previous cytotoxic chemotherapy
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